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Masuda T, Okada H, Nagata D. Comparative impact of hemodialysis and isolated ultrafiltration on vascular endothelial glycocalyx injury. Ther Apher Dial 2025. [PMID: 40241503 DOI: 10.1111/1744-9987.70027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 04/18/2025]
Affiliation(s)
- Takahiro Masuda
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Japan
| | - Hideshi Okada
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Daisuke Nagata
- Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Japan
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2
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Yamaji F, Fukuta T, Ichihashi M, Mizuno Y, Suzuki K, Miyake T, Kanda N, Okada H. Effectiveness of syndecan-1 as an adjunct diagnostic marker in small bowel injury: a report of two cases. Trauma Surg Acute Care Open 2025; 10:e001727. [PMID: 39897379 PMCID: PMC11784201 DOI: 10.1136/tsaco-2024-001727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 01/04/2025] [Indexed: 02/04/2025] Open
Abstract
Background Small bowel injuries are rare in trauma. Diagnosing these injuries is difficult owing to the lack of clear signs, and delays in diagnosis might increase complications and mortality. Trauma can damage the vascular endothelial glycocalyx, with syndecan-1 emerging as a marker of injury. Here, we describe two cases of small bowel injury due to traffic motor vehicle crash trauma. Case presentation The patients, one in their 40s and one teenaged, were transported to our hospital after a traffic motor vehicle crash. Both patients were wearing seat belts at the time of the motor vehicle crash, and the car's airbags deployed properly. Their vital signs were stable at admission, and non-operative treatment was selected. However, their abdominal pain did not improve, and based on posthospitalization CT reconstructive imaging, intra-abdominal hemorrhage was suspected. Surgery was performed, revealing small intestinal injuries. In both patients, a high serum syndecan-1 level in the blood test at admission was a common characteristic. Conclusion Increased serum syndecan-1 level was observed in blood tests during the initial treatment of small intestinal injuries in these patients, suggesting its potential utility in early diagnosis. However, further accumulation of cases and detailed studies are required to substantiate these results.
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Affiliation(s)
- Fuminori Yamaji
- Gifu University Hospital, Gifu, Japan
- Department of Emergency and Disaster Medicine, Gifu University School of Medicine Graduate School of Medicine, Gifu, Gifu Prefecture, Japan
| | - Tetsuya Fukuta
- Gifu University Hospital, Gifu, Japan
- Department of Emergency and Disaster Medicine, Gifu University School of Medicine Graduate School of Medicine, Gifu, Gifu Prefecture, Japan
| | - Masahiro Ichihashi
- Gifu University Hospital, Gifu, Japan
- Department of Emergency and Disaster Medicine, Gifu University School of Medicine Graduate School of Medicine, Gifu, Gifu Prefecture, Japan
| | - Yosuke Mizuno
- Gifu University Hospital, Gifu, Japan
- Department of Emergency and Disaster Medicine, Gifu University School of Medicine Graduate School of Medicine, Gifu, Gifu Prefecture, Japan
| | - Keiko Suzuki
- Gifu University Hospital, Gifu, Japan
- Gifu Pharmaceutical University, Gifu, Japan
| | - Takahito Miyake
- Gifu University Hospital, Gifu, Japan
- Department of Emergency and Disaster Medicine, Gifu University School of Medicine Graduate School of Medicine, Gifu, Gifu Prefecture, Japan
| | - Norihide Kanda
- Gifu University Hospital, Gifu, Japan
- Department of Emergency and Disaster Medicine, Gifu University School of Medicine Graduate School of Medicine, Gifu, Gifu Prefecture, Japan
| | - Hideshi Okada
- Department of Emergency and Disaster Medicine, Gifu University School of Medicine Graduate School of Medicine, Gifu, Gifu Prefecture, Japan
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Kitasato L, Yamaoka-Tojo M, Iwaya T, Murayama Y, Ikeda Y, Hashikata T, Oikawa J, Suzuki M, Misawa N, Kawashima R, Ogawa F, Ako J. Rivaroxaban as a Protector of Oxidative Stress-Induced Vascular Endothelial Glycocalyx Damage via the IQGAP1/PAR1-2/PI3K/Akt Pathway. J Vasc Res 2024; 62:22-36. [PMID: 39496251 PMCID: PMC11797952 DOI: 10.1159/000542419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 10/30/2024] [Indexed: 11/06/2024] Open
Abstract
INTRODUCTION The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a factor X inhibitor, on the glycocalyx under oxidative stress condition. METHODS We examined the impact of rivaroxaban on human umbilical vein endothelial cells exposed to acute and chronic H2O2-induced oxidative stress. RESULTS Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx. CONCLUSION We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention. INTRODUCTION The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a factor X inhibitor, on the glycocalyx under oxidative stress condition. METHODS We examined the impact of rivaroxaban on human umbilical vein endothelial cells exposed to acute and chronic H2O2-induced oxidative stress. RESULTS Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx. CONCLUSION We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.
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Affiliation(s)
- Lisa Kitasato
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Minako Yamaoka-Tojo
- Department of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara, Japan
| | - Toshiyuki Iwaya
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan
- Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
| | - Yusuke Murayama
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan
- Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan
| | - Yuki Ikeda
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Takehiro Hashikata
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Jun Oikawa
- Department of Kitasato Clinical Research Center, Kitasato University School of Medicine, Sagamihara, Japan
| | - Machika Suzuki
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Nonoka Misawa
- Department of Regulation Biochemistry, Kitasato University School of Allied Health Sciences, Sagamihara, Japan
| | - Rei Kawashima
- Department of Regulation Biochemistry, Kitasato University School of Allied Health Sciences, Sagamihara, Japan
| | - Fumihiro Ogawa
- Department of Emergency Medicine, School of Medicine, Yokohama City University, Yokohama, Japan
| | - Junya Ako
- Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan
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Seki K, Sueyoshi K, Miyoshi Y, Nakamura Y, Ishihara T, Kondo Y, Kuroda Y, Yonekura A, Iwabuchi K, Okamoto K, Tanaka H. Complement activation and lung injury in Japanese patients with COVID-19: a prospective observational study. Sci Rep 2024; 14:24895. [PMID: 39438600 PMCID: PMC11496683 DOI: 10.1038/s41598-024-76365-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 10/14/2024] [Indexed: 10/25/2024] Open
Abstract
Background The production of inflammatory cytokines is reportedly increased in patients with coronavirus disease 2019 (COVID-19), causing the migration of neutrophils and monocytes to lung tissues. This disrupts the air-blood barrier by damaging the bronchial epithelial and vascular endothelial cells. As multiorgan dysfunction in sepsis is considered to be partly caused by complement activation, which can cause lung injury in patients with COVID-19. There are limited studies examining the link between complement activation in patients with COVID-19. This study aimed to AQinvestigate the association of complement activation with the pathophysiology of COVID-19. Twenty-seven patients with COVID-19 were enrolled in this study and classified into two groups depending on the indication for mechanical ventilation. Plasma complement factors (C3a, C5a, Ba, and sC5b-9), complement regulators (sCD59 and factor H), interleukin-6 (IL-6), and syndecan-1 levels were measured using Enzyme-linked immunosorbent assay (ELISA). Results: All complement factors and regulators, IL-6, and syndecan-1 levels were significantly elevated in patients with COVID-19 compared with those in healthy controls. C5a and sC5b-9 levels were decreased significantly in the invasive mechanical ventilation (IMV) group compared with those in the non-IMV group. Syndecan-1 levels were significantly increased in the IMV group compared with those in the non-IMV group. Conclusions: Complement activation is an exacerbating factor for lung injury in patients with COVID-19. Complement factors are nonessential predictors of mechanical ventilation; however, syndecan-1 could be a biomarker of COVID-19 severity in patients.
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Affiliation(s)
- Kentaro Seki
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan
| | - Koichiro Sueyoshi
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan.
| | - Yukari Miyoshi
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan
| | - Yuki Nakamura
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan
| | - Tadashi Ishihara
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan
| | - Yutaka Kondo
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan
| | - Yoko Kuroda
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan
| | - Ayumi Yonekura
- Institute for Environmental and Gender Specific Medicine, Juntendo University, Urayasu, Chiba, Japan
| | - Kazuhisa Iwabuchi
- Institute for Environmental and Gender Specific Medicine, Juntendo University, Urayasu, Chiba, Japan
| | - Ken Okamoto
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan
| | - Hiroshi Tanaka
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Urayasu, Chiba, Japan
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Lian H, Cai H, Zhang H, Zhang Y, Wang X. Inflammation, immunity and biomarkers in procoagulant responses of critically ill patients. Am J Transl Res 2024; 16:5797-5812. [PMID: 39544782 PMCID: PMC11558399 DOI: 10.62347/edar9565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 09/26/2024] [Indexed: 11/17/2024]
Abstract
Understanding the pathobiology of critical illness is essential for patients' prognosis. Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. As part of the host response, procoagulant responses, one of the most primitive reactions in biology, start at the very beginning of diseases and can be monitored throughout the process. Currently, we can achieve near-complete monitoring of the coagulation process, and procoagulant responses serve as indicators of the severity of host response in critically ill patients. However, the rapid interpretation of the complex results of various biomarkers remains a challenge for many clinicians. The indicators commonly used for coagulation assessment are complex, typically divided into three categories for clarity: process index, functional index, and outcome index. Monitoring and understanding these indicators can help manage procoagulant responses. The intervention of procoagulant response should be part of the bundle therapy, alongside the treatment for primary disease, management for hemodynamics, and controlling for host response. Early intervention for procoagulant response mainly includes anti-inflammation, antiplatelet and anticoagulant therapy, as well as management of primary disease. In this review, we systemically introduce the onset, assessment and intervention of procoagulant response.
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Affiliation(s)
- Hui Lian
- Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730, China
| | - Huacong Cai
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730, China
| | - Hongmin Zhang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730, China
| | - Yan Zhang
- Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730, China
| | - Xiaoting Wang
- Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730, China
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Margaret MS, Melrose J. Impaired instructive and protective barrier functions of the endothelial cell glycocalyx pericellular matrix is impacted in COVID-19 disease. J Cell Mol Med 2024; 28:e70033. [PMID: 39180511 PMCID: PMC11344469 DOI: 10.1111/jcmm.70033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 05/29/2024] [Accepted: 06/18/2024] [Indexed: 08/26/2024] Open
Abstract
The aim of this study was to review the roles of endothelial cells in normal tissue function and to show how COVID-19 disease impacts on endothelial cell properties that lead to much of its associated symptomatology. This places the endothelial cell as a prominent cell type to target therapeutically in the treatment of this disorder. Advances in glycosaminoglycan analytical techniques and functional glycomics have improved glycosaminoglycan mimetics development, providing agents that can more appropriately target various aspects of the behaviour of the endothelial cell in-situ and have also provided polymers with potential to prevent viral infection. Thus, promising approaches are being developed to combat COVID-19 disease and the plethora of symptoms this disease produces. Glycosaminoglycan mimetics that improve endothelial glycocalyx boundary functions have promising properties in the prevention of viral infection, improve endothelial cell function and have disease-modifying potential. Endothelial cell integrity, forming tight junctions in cerebral cell populations in the blood-brain barrier, prevents the exposure of the central nervous system to circulating toxins and harmful chemicals, which may contribute to the troublesome brain fogging phenomena reported in cognitive processing in long COVID disease.
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Affiliation(s)
- M. Smith Margaret
- Raymond Purves Bone and Joint Research LaboratoryKolling Institute, Northern Sydney Local Health DistrictSt. LeonardsNew South WalesAustralia
- Arthropharm Australia Pharmaceuticals Pty LtdBondi JunctionSydneyNew South WalesAustralia
| | - James Melrose
- Raymond Purves Bone and Joint Research LaboratoryKolling Institute, Northern Sydney Local Health DistrictSt. LeonardsNew South WalesAustralia
- Graduate School of Biomedical EngineeringUniversity of New South WalesSydneyNew South WalesAustralia
- Sydney Medical SchoolNorthern, The University of SydneySydneyNew South WalesAustralia
- Faculty of Medicine and HealthThe University of Sydney, Royal North Shore HospitalSt. LeonardsNew South WalesAustralia
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Kong G, Li D, Liu X, Feng J, Ning F, Huang X, Qi B, Qu J, Wang X. PLD2 deficiency alleviates endothelial glycocalyx degradation in LPS-induced ARDS/ALI. Biochem Biophys Res Commun 2024; 716:150019. [PMID: 38703555 DOI: 10.1016/j.bbrc.2024.150019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 04/20/2024] [Accepted: 04/25/2024] [Indexed: 05/06/2024]
Abstract
- Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a life-threatening condition marked by severe lung inflammation and increased lung endothelial barrier permeability. Endothelial glycocalyx deterioration is the primary factor of vascular permeability changes in ARDS/ALI. Although previous studies have shown that phospholipase D2 (PLD2) is closely related to the onset and progression of ARDS/ALI, its role and mechanism in the damage of endothelial cell glycocalyx remains unclear. We used LPS-induced ARDS/ALI mice (in vivo) and LPS-stimulated injury models of EA.hy926 endothelial cells (in vitro). We employed C57BL/6 mice, including wild-type and PLD2 knockout (PLD2-/-) mice, to establish the ARDS/ALI model. We applied immunofluorescence and ELISA to examine changes in syndecan-1 (SDC-1), matrix metalloproteinase-9 (MMP9), inflammatory cytokines (TNF-α, IL-6, and IL-1β) levels and the effect of external factors, such as phosphatidic acid (PA), 1-butanol (a PLD inhibitor), on SDC-1 and MMP9 expression levels. We found that PLD2 deficiency inhibits SDC-1 degradation and MMP9 expression in LPS-induced ARDS/ALI. Externally added PA decreases SDC-1 levels and increases MMP9 in endothelial cells, hence underlining PA's role in SDC-1 degradation. Additionally, PLD2 deficiency decreases the production of inflammatory cytokines (TNF-α, IL-6, and IL-1β) in LPS-induced ARDS/ALI. In summary, these findings suggest that PLD2 deficiency plays a role in inhibiting the inflammatory process and protecting against endothelial glycocalyx injury in LPS-induced ARDS/ALI.
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Affiliation(s)
- Guiqing Kong
- Department of Intensive Care Unit, Binzhou Medical University Hospital, Binzhou, 256603, Shandong Province, China
| | - Dongxiao Li
- Department of Intensive Care Unit, Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, 264000, Shandong Province, China
| | - Xiangyong Liu
- Department of Cell Biology, Binzhou Medical University, Yantai, 264003, Shandong Province, China.
| | - Jiali Feng
- Department of Pulmonary and Critical Care Medicine, Yantaishan Hospital, Yantai, 264000, Shandong Province, China
| | - Fangyu Ning
- Department of Intensive Care Unit, Binzhou Medical University Hospital, Binzhou, 256603, Shandong Province, China
| | - Xiao Huang
- Department of Intensive Care Unit, Binzhou Medical University Hospital, Binzhou, 256603, Shandong Province, China
| | - Boyang Qi
- Department of Cardiovascular Surgery Intensive Care Unit, Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, 264000, Shandong Province, China
| | - Jianyu Qu
- Department of Critical Care Medicine, Yantaishan Hospital, Yantai, 264000, Shandong Province, China
| | - Xiaozhi Wang
- Department of Intensive Care Unit, Binzhou Medical University Hospital, Binzhou, 256603, Shandong Province, China.
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Ider M, Ceylan C, Naseri A, Ceylan O, Durgut MK, Ok M, Iyigun SS, Erol BB, Sahin HB, Kilickaya MC. Evaluation of endothelial glycocalyx injury biomarkers in feline hemotropic mycoplasmosis. Sci Rep 2024; 14:12931. [PMID: 38839816 PMCID: PMC11153643 DOI: 10.1038/s41598-024-62359-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 05/16/2024] [Indexed: 06/07/2024] Open
Abstract
The present study aimed to investigate endothelial glycocalyx (eGCx) damage in cats with feline hemotropic mycoplasmosis caused by Mycoplasma haemofelis using selected biomarkers and to determine the diagnostic and prognostic significance of these biomarkers. The study included 25 cats with feline hemotropic mycoplasmosis and 10 healthy cats. Clinical examination, blood gas analysis, complete blood count, and biochemical analysis were performed. Hemotropic mycoplasmosis diagnosed by microscopic examination and molecularly confirmed by PCR targeting the Mycoplasma haemofelis 16s rRNA gene. To evaluate endothelial glycocalyx damage, syndecan-1, endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), and vascular endothelial growth factor-A (VEGF-A) concentrations were measured using cat-specific commercial ELISA kits. Of the cats with feline hemotropic mycoplasmosis, 14 (56%) survived and 11 (44%) died. While syndecan-1 and ET-1 concentrations were significantly higher in cats with hemotropic mycoplasmosis compared to the control group (p < 0.001), no statistically significant difference was found for ADMA and VEGF-A concentrations (p > 0.05). Endothelial glycocalyx biomarkers showed significant correlations with each other and with hematological parameters (p < 0.01). The results of the ROC analysis showed that ET-1 with area under the curve (AUC) of 0.821 (p < 0.01) and VEGF-A with AUC of 0.805 (p < 0.010) were found to be significant prognostic indicators. In conclusion, this study demonstrated that serum syndecan-1 and ET-1 can be used as diagnostic and serum ET-1 and VEGF-A as prognostic biomarkers in cats with hemotropic mycoplasmosis. Our results indicate the development of eGCx damage in feline hemotropic mycoplasmosis and suggest that glycocalyx disruption may contribute to the pathogenesis of the disease.
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Affiliation(s)
- Merve Ider
- Department of Internal Medicine, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey.
| | - Ceylan Ceylan
- Department of Parasitology, Faculty of Veterinary Medicine, Siirt University, Siirt, Turkey
| | - Amir Naseri
- Department of Internal Medicine, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey
| | - Onur Ceylan
- Department of Parasitology, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey
| | - Murat Kaan Durgut
- Department of Internal Medicine, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey
| | - Mahmut Ok
- Department of Internal Medicine, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey
| | - Suleyman Serhat Iyigun
- Department of Internal Medicine, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey
| | - Busra Burcu Erol
- Department of Internal Medicine, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey
| | - Hatice Betul Sahin
- Department of Internal Medicine, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey
| | - Merve Cansu Kilickaya
- Department of Internal Medicine, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey
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Kuroda T, Suzuki A, Okada H, Shimizu M, Watanabe D, Suzuki K, Mori K, Ohmura K, Niwa A, Imaizumi Y, Matsuo M, Ichihashi K, Okubo T, Taniguchi T, Kanayma T, Kobayashi R, Sugie S, Hara A, Tomita H. Endothelial Glycocalyx in the Peripheral Capillaries is Injured Under Oxaliplatin-Induced Neuropathy. THE JOURNAL OF PAIN 2024; 25:104462. [PMID: 38211844 DOI: 10.1016/j.jpain.2024.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 12/02/2023] [Accepted: 01/03/2024] [Indexed: 01/13/2024]
Abstract
Oxaliplatin, a platinum-based anticancer drug, is associated with peripheral neuropathy (oxaliplatin-induced peripheral neuropathy, OIPN), which can lead to worsening of quality of life and treatment interruption. The endothelial glycocalyx, a fragile carbohydrate-rich layer covering the luminal surface of endothelial cells, acts as an endothelial gatekeeper and has been suggested to protect nerves, astrocytes, and other cells from toxins and substances released from the capillary vessels. Mechanisms underlying OIPN and the role of the glycocalyx remain unclear. This study aimed to define changes in the three-dimensional ultrastructure of capillary endothelial glycocalyx near nerve fibers in the hind paws of mice with OIPN. The mouse model of OPIN revealed disruption of the endothelial glycocalyx in the peripheral nerve compartment, accompanied by vascular permeability, edema, and damage to the peripheral nerves. To investigate the potential treatment interventions, nafamostat mesilate, a glycocalyx protective agent was used in tumor-bearing male mice. Nafamostat mesilate suppressed mechanical allodynia associated with neuropathy. It also prevented intra-epidermal nerve fiber loss and improved vascular permeability in the peripheral paws. The disruption of endothelial glycocalyx in the capillaries that lie within peripheral nerve bundles is a novel finding in OPIN. Furthermore, these findings point toward the potential of a new treatment strategy targeting endothelial glycocalyx to prevent vascular injury as an effective treatment of neuropathy as well as of many other diseases. PERSPECTIVE: OIPN damages the endothelial glycocalyx in the peripheral capillaries, increasing vascular permeability. In order to prevent OIPN, this work offers a novel therapy approach that targets endothelial glycocalyx.
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Affiliation(s)
- Takahiro Kuroda
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Akio Suzuki
- Department of Pharmacy, Gifu University Hospital, Gifu, Japan; Laboratory of Advanced Medical Pharmacy, Gifu Pharmaceutical University, Gifu, Japan
| | - Hideshi Okada
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan; Center for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Study, Gifu, Japan
| | - Masayoshi Shimizu
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Daichi Watanabe
- Department of Pharmacy, Gifu University Hospital, Gifu, Japan
| | - Keiko Suzuki
- Department of Pharmacy, Gifu University Hospital, Gifu, Japan; Department of Infection Control, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Kosuke Mori
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan; Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Kazufumi Ohmura
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan; Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Ayumi Niwa
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yuko Imaizumi
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Mikiko Matsuo
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Koki Ichihashi
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Takafumi Okubo
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Toshiaki Taniguchi
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Tomohiro Kanayma
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Ryo Kobayashi
- Department of Pharmacy, Gifu University Hospital, Gifu, Japan; Laboratory of Advanced Medical Pharmacy, Gifu Pharmaceutical University, Gifu, Japan
| | - Shigeyuki Sugie
- Department of Pathology, Asahi University Hospital, Gifu, Japan
| | - Akira Hara
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hiroyuki Tomita
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan; Center for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Study, Gifu, Japan
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Miyazaki A, Hokka M, Obata N, Mizobuchi S. Perioperative serum syndecan-1 concentrations in patients who underwent cardiovascular surgery with cardiopulmonary bypass and its association with the occurrence of postoperative acute kidney injury: a retrospective observational study. BMC Anesthesiol 2024; 24:154. [PMID: 38649813 PMCID: PMC11034048 DOI: 10.1186/s12871-024-02546-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 04/17/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Various factors can cause vascular endothelial damage during cardiovascular surgery (CVS) with cardiopulmonary bypass (CPB), which has been suggested to be associated with postoperative complications. However, few studies have specifically investigated the relationship between the degree of vascular endothelial damage and postoperative acute kidney injury (pAKI). The objectives of this study were to measure perioperative serum syndecan-1 concentrations in patients who underwent CVS with CPB, evaluate their trends, and determine their association with pAKI. METHODS This was a descriptive and case‒control study conducted at the National University Hospital. Adult patients who underwent CVS with CPB at a national university hospital between March 15, 2016, and August 31, 2020, were included. Patients who were undergoing preoperative dialysis, had preoperative serum creatinine concentrations greater than 2.0 mg dl-1, who were undergoing surgery involving the descending aorta were excluded. The perioperative serum syndecan-1 concentration was measured, and its association with pAKI was investigated. RESULTS Fifty-two patients were included. pAKI occurred in 18 (34.6%) of those patients. The serum syndecan-1 concentration increased after CPB initiation and exhibited bimodal peak values. The serum syndecan-1 concentration at all time points was significantly elevated compared to that after the induction of anesthesia. The serum syndecan-1 concentration at 30 min after weaning from CPB and on postoperative day 1 was associated with the occurrence of pAKI (OR = 1.10 [1.01 to 1.21], P = 0.03]; OR = 1.16 [1.01 to 1.34], P = 0.04]; and the cutoff values of the serum syndecan-1 concentration that resulted in pAKI were 101.0 ng ml-1 (sensitivity = 0.71, specificity = 0.62, area under the curve (AUC) = 0.67 (0.51 to 0.83)) and 57.1 ng ml-1 (sensitivity = 0.82, specificity = 0.56, AUC = 0.71 (0.57 to 0.86)). Multivariate logistic regression analysis revealed that the serum syndecan-1 concentration on postoperative day 1 was associated with the occurrence of pAKI (OR = 1.02 [1.00 to 1.03]; P = 0.03). CONCLUSION The serum syndecan-1 concentration at all time points was significantly greater than that after the induction of anesthesia. The serum syndecan-1 concentration on postoperative day 1 was significantly associated with the occurrence of pAKI. TRIAL REGISTRATION This study is not a clinical trial and is not registered with the registry.
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Affiliation(s)
- Atsushi Miyazaki
- Division of Anesthesiology, Department of Surgery Related, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki Cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan
| | - Mai Hokka
- Division of Anesthesiology, Department of Surgery Related, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki Cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan.
| | - Norihiko Obata
- Division of Anesthesiology, Department of Surgery Related, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki Cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan
| | - Satoshi Mizobuchi
- Division of Anesthesiology, Department of Surgery Related, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki Cho, Chuo-Ku, Kobe, Hyogo, 650-0017, Japan
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Brill JB, Mueck KM, Cotton ME, Tang B, Sandoval M, Kao LS, Cotton BA. Impact of COVID status and blood group on complications in patients in hemorrhagic shock. Trauma Surg Acute Care Open 2024; 9:e001250. [PMID: 38529316 PMCID: PMC10961517 DOI: 10.1136/tsaco-2023-001250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 02/23/2024] [Indexed: 03/27/2024] Open
Abstract
Objective Among critically injured patients of various blood groups, we sought to compare survival and complication rates between COVID-19-positive and COVID-19-negative cohorts. Background SARS-CoV-2 infections have been shown to cause endothelial injury and dysfunctional coagulation. We hypothesized that, among patients with trauma in hemorrhagic shock, COVID-19-positive status would be associated with increased mortality and inpatient complications. As a secondary hypothesis, we suspected group O patients with COVID-19 would experience fewer complications than non-group O patients with COVID-19. Methods We evaluated all trauma patients admitted 4/2020-7/2020. Patients 16 years or older were included if they presented in hemorrhagic shock and received emergency release blood products. Patients were dichotomized by COVID-19 testing and then divided by blood groups. Results 3281 patients with trauma were evaluated, and 417 met criteria for analysis. Seven percent (29) of patients were COVID-19 positive; 388 were COVID-19 negative. COVID-19-positive patients experienced higher complication rates than the COVID-19-negative cohort, including acute kidney injury, pneumonia, sepsis, venous thromboembolism, and systemic inflammatory response syndrome. Univariate analysis by blood groups demonstrated that survival for COVID-19-positive group O patients was similar to that of COVID-19-negative patients (79 vs 78%). However, COVID-19-positive non-group O patients had a significantly lower survival (38%). Controlling for age, sex and Injury Severity Score, COVID-19-positive patients had a greater than 70% decreased odds of survival (OR 0.28, 95% CI 0.09 to 0.81; p=0.019). Conclusions COVID-19 status is associated with increased major complications and 70% decreased odds of survival in this group of patients with trauma. However, among patients with COVID-19, blood group O was associated with twofold increased survival over other blood groups. This survival rate was similar to that of patients without COVID-19.
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Affiliation(s)
- Jason Bradley Brill
- Department of Surgery, McGovern Medical School at University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Krislynn M Mueck
- Department of Surgery, McGovern Medical School at University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Madeline E Cotton
- Department of Surgery, McGovern Medical School at University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Brian Tang
- Department of Surgery, McGovern Medical School at University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Mariela Sandoval
- Department of Surgery, McGovern Medical School at University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Lillian S Kao
- Department of Surgery, McGovern Medical School at University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Bryan A Cotton
- Department of Surgery, McGovern Medical School at University of Texas Health Science Center at Houston, Houston, Texas, USA
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Hieba AR, Arida EA, Osman HAH, Imbaby SAEDM, Moharem HAHA. Endothelial glycocalyx shedding during active COVID-19 infection and its effect on disease severity. EGYPTIAN JOURNAL OF ANAESTHESIA 2023. [DOI: 10.1080/11101849.2023.2192099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2023] Open
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13
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AlNafea HM, Korish AA. The interplay between hypovitaminosis D and the immune dysfunction in the arteriovenous thrombotic complications of the sever coronavirus disease 2019 (COVID-19) infection. Blood Coagul Fibrinolysis 2023; 34:129-137. [PMID: 36966750 PMCID: PMC10089932 DOI: 10.1097/mbc.0000000000001212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 02/11/2023] [Indexed: 03/28/2023]
Abstract
Thromboembolic complications including cerebrovascular accidents, pulmonary embolism, myocardial infarction, deep vein thrombosis and disseminating intravascular coagulopathy are serious encounters in sever coronavirus disease 2019 (COVID-19) infected patients. This worsens the prognosis and may lead to death or life long morbidities. The laboratory finding of the disturbed haemostasias and the hyperinflammatory response are almost invariably present in COVID-19 patients. Multiple treatment modalities are utilized by the healthcare professionals to overcome the cytokine storm, oxidative stress, endothelial dysfunction, and coagulopathy in these patients. The combined actions of vitamin D (VitD) as a steroid hormone with anti-inflammatory, immunomodulatory, and antithrombotic properties increase the potential of the possible involvement of hypovitaminosis D in the thromboembolic complications of COVID-19 infection, and stimulated researchers and physicians to administer VitD therapy to prevent the infection and/or overcome the disease complications. The current review highlighted the immunomodulatory, anti-inflammatory, antioxidative and hemostatic functions of VitD and its interrelation with the renin-angiotensin-aldosterone system (RAAS) pathway and the complement system. Additionally, the association of VitD deficiency with the incidence and progression of COVID-19 infection and the associated cytokine storm, oxidative stress, hypercoagulability, and endothelial dysfunction were emphasized. Normalizing VitD levels by daily low dose therapy in patients with hypovitaminosis D below (25 nmol/l) is essential for a balanced immune response and maintaining the health of the pulmonary epithelium. It protects against upper respiratory tract infections and decreases the complications of COVID-19 infections. Understanding the role of VitD and its associated molecules in the protection against the coagulopathy, vasculopathy, inflammation, oxidative stress and endothelial dysfunction in COVID-19 infection could lead to new therapeutic strategies to prevent, treat, and limit the complications of this deadly virus infection.
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Affiliation(s)
- Haifa M. AlNafea
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University
| | - Aida A. Korish
- Physiology Department (29), College of Medicine, King Saud University Medical City (KSUMC), King Saud university, Riyadh, Saudi Arabia
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Xu SW, Ilyas I, Weng JP. Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies. Acta Pharmacol Sin 2023; 44:695-709. [PMID: 36253560 PMCID: PMC9574180 DOI: 10.1038/s41401-022-00998-0] [Citation(s) in RCA: 183] [Impact Index Per Article: 91.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 09/11/2022] [Indexed: 12/15/2022]
Abstract
The fight against coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is still raging. However, the pathophysiology of acute and post-acute manifestations of COVID-19 (long COVID-19) is understudied. Endothelial cells are sentinels lining the innermost layer of blood vessel that gatekeep micro- and macro-vascular health by sensing pathogen/danger signals and secreting vasoactive molecules. SARS-CoV-2 infection primarily affects the pulmonary system, but accumulating evidence suggests that it also affects the pan-vasculature in the extrapulmonary systems by directly (via virus infection) or indirectly (via cytokine storm), causing endothelial dysfunction (endotheliitis, endothelialitis and endotheliopathy) and multi-organ injury. Mounting evidence suggests that SARS-CoV-2 infection leads to multiple instances of endothelial dysfunction, including reduced nitric oxide (NO) bioavailability, oxidative stress, endothelial injury, glycocalyx/barrier disruption, hyperpermeability, inflammation/leukocyte adhesion, senescence, endothelial-to-mesenchymal transition (EndoMT), hypercoagulability, thrombosis and many others. Thus, COVID-19 is deemed as a (micro)vascular and endothelial disease. Of translational relevance, several candidate drugs which are endothelial protective have been shown to improve clinical manifestations of COVID-19 patients. The purpose of this review is to provide a latest summary of biomarkers associated with endothelial cell activation in COVID-19 and offer mechanistic insights into the molecular basis of endothelial activation/dysfunction in macro- and micro-vasculature of COVID-19 patients. We envisage further development of cellular models and suitable animal models mimicking endothelial dysfunction aspect of COVID-19 being able to accelerate the discovery of new drugs targeting endothelial dysfunction in pan-vasculature from COVID-19 patients.
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Affiliation(s)
- Suo-Wen Xu
- Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, 230001, China.
| | - Iqra Ilyas
- Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, 230001, China
| | - Jian-Ping Weng
- Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, 230001, China.
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15
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Izzo C, Visco V, Gambardella J, Ferruzzi GJ, Rispoli A, Rusciano MR, Toni AL, Virtuoso N, Carrizzo A, Di Pietro P, Iaccarino G, Vecchione C, Ciccarelli M. Cardiovascular Implications of microRNAs in Coronavirus Disease 2019. J Pharmacol Exp Ther 2023; 384:102-108. [PMID: 35779946 DOI: 10.1124/jpet.122.001210] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 06/11/2022] [Accepted: 06/15/2022] [Indexed: 01/13/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to be a global challenge due to resulting morbidity and mortality. Cardiovascular (CV) involvement is a crucial complication in coronavirus disease 2019 (COVID-19), and no strategies are available to prevent or specifically address CV events in COVID-19 patients. The identification of molecular partners contributing to CV manifestations in COVID-19 patients is crucial for providing early biomarkers, prognostic predictors, and new therapeutic targets. The current report will focus on the role of microRNAs (miRNAs) in CV complications associated with COVID-19. Indeed, miRNAs have been proposed as valuable biomarkers and predictors of both cardiac and vascular damage occurring in SARS-CoV-2 infection. SIGNIFICANCE STATEMENT: It is essential to identify the molecular mediators of coronavirus disease 2019 (COVID-19) cardiovascular (CV) complications. This report focused on the role of microRNAs in CV complications associated with COVID-19, discussing their potential use as biomarkers, prognostic predictors, and therapeutic targets.
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Affiliation(s)
- Carmine Izzo
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Valeria Visco
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Jessica Gambardella
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Germano Junior Ferruzzi
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Antonella Rispoli
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Maria Rosaria Rusciano
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Anna Laura Toni
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Nicola Virtuoso
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Albino Carrizzo
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Paola Di Pietro
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Guido Iaccarino
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Carmine Vecchione
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
| | - Michele Ciccarelli
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy (C.I., V.V., G.J.F., A.R., M.R.R., A.L.T., A.C., P.D.P., C.V., M.C.); Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy (J.G., G.I.); Department of Medicine, Einstein-Sinai Diabetes Research Center, The Fleischer Institute for Diabetes and Metabolism, Einstein Institute for Aging Research, Albert Einstein College of Medicine, New York, New York (J.G.); Cardiology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona," Salerno, Italy (N.V.); and Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy (A.C., C.V.)
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Netiazhenko VZ, Mostovyi SI, Safonova OM, Mikhaliev KO. MICROCIRCULATORY ALTERATIONS IN STABLE CORONARY ARTERY DISEASE PATIENTS WITH CONCOMITANT COVID-19. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2023; 76:2224-2238. [PMID: 37948719 DOI: 10.36740/wlek202310115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
OBJECTIVE The aim: To evaluate the alterations in microcirculation of stable coronary artery disease (SCAD) patients with concomitant COVID-19. PATIENTS AND METHODS Materials and methods: The cross-sectional study analyzed the data from 80 patients, being subdivided as follows: group 1 (G1) - SCAD without COVID-19 (n=30); group 2 (G2) - SCAD with concomitant COVID-19 (n=25); group 3 (G3) - COVID-19 without SCAD (n=25). The control group included 30 relatively healthy volunteers. The state of microcirculation was assessed by nailfold videocapillaroscopy (NVC) and laser Doppler flowmetry (LDF). RESULTS Results: NVC data from G2 revealed the sings of capillary bed remodeling, along with the most pronounced decrease in capillary (arteriolar part of the loop) blood flow velocity (vs. G1 and G3). LDF data from G2 were evident for the alterations in both endothelium-dependent and -independent mechanisms of microvascular flow regulation. The 72 % of G2 constituted the cases of microcirculatory hemodynamic «congestion-stasis» (MHCS) type (characterized by the decreased laser Doppler perfusion index and reduced endothelium-dependent microvascular reactivity [MVR]), and the cases of mixed type with reduced MVR. The pooled hyporeactive profile (of both MHCS type and a mixed type with reduced MVR) demonstrated the higher frequency of G2 patients (40 %), as against 11 % in the pooled alternative hemodynamic group (p<0,001) (included 80 % of cases with preserved MVR). CONCLUSION Conclusions: G2 profile demonstrated the predomination of patients, possessing a MHCS type or a mixed type with reduced MVR. The pooled microcirculatory hyporeactive profile was presented with G2 cases to a greater extent, than in the pooled profile with predominantly preserved MVR.
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Affiliation(s)
- Vasyl Z Netiazhenko
- BOGOMOLETS NATIONAL MEDICAL UNIVERSITY, KYIV, UKRAINE; STATE INSTITUTION OF SCIENCE «RESEARCH AND PRACTICAL CENTER OF PREVENTIVE AND CLINICAL MEDICINE» STATE ADMINISTRATIVE DEPARTMENT, KYIV, UKRAINE
| | - Serhii I Mostovyi
- BOGOMOLETS NATIONAL MEDICAL UNIVERSITY, KYIV, UKRAINE; SE «MEDBUD», KYIV, UKRAINE
| | | | - Kyrylo O Mikhaliev
- STATE INSTITUTION OF SCIENCE «RESEARCH AND PRACTICAL CENTER OF PREVENTIVE AND CLINICAL MEDICINE» STATE ADMINISTRATIVE DEPARTMENT, KYIV, UKRAINE
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17
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Fatmi A, Saadi W, Beltrán-García J, García-Giménez JL, Pallardó FV. The Endothelial Glycocalyx and Neonatal Sepsis. Int J Mol Sci 2022; 24:364. [PMID: 36613805 PMCID: PMC9820255 DOI: 10.3390/ijms24010364] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 12/12/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022] Open
Abstract
Sepsis carries a substantial risk of morbidity and mortality in newborns, especially preterm-born neonates. Endothelial glycocalyx (eGC) is a carbohydrate-rich layer lining the vascular endothelium, with important vascular barrier function and cell adhesion properties, serving also as a mechano-sensor for blood flow. eGC shedding is recognized as a fundamental pathophysiological process generating microvascular dysfunction, which in turn contributes to multiple organ failure and death in sepsis. Although the disruption of eGC and its consequences have been investigated intensively in the adult population, its composition, development, and potential mechanisms of action are still poorly studied during the neonatal period, and more specifically, in neonatal sepsis. Further knowledge on this topic may provide a better understanding of the molecular mechanisms that guide the sepsis pathology during the neonatal period, and would increase the usefulness of endothelial glycocalyx dysfunction as a diagnostic and prognostic biomarker. We reviewed several components of the eGC that help to deeply understand the mechanisms involved in the eGC disruption during the neonatal period. In addition, we evaluated the potential of eGC components as biomarkers and future targets to develop therapeutic strategies for neonatal sepsis.
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Affiliation(s)
- Ahlam Fatmi
- INCLIVA Health Research Institute, Mixed Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain
| | - Wiam Saadi
- Department of Biology, Faculty of Nature, Life and Earth Sciences, University of Djillali Bounaama, Khemis Miliana 44225, Algeria
| | - Jesús Beltrán-García
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, 46010 Valencia, Spain
- Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, 46010 Valencia, Spain
- Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, CA 92093, USA
| | - José Luis García-Giménez
- INCLIVA Health Research Institute, Mixed Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, 46010 Valencia, Spain
- Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, 46010 Valencia, Spain
| | - Federico V. Pallardó
- INCLIVA Health Research Institute, Mixed Unit for Rare Diseases INCLIVA-CIPF, 46010 Valencia, Spain
- Center for Biomedical Network Research on Rare Diseases (CIBERER), Institute of Health Carlos III, 46010 Valencia, Spain
- Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, 46010 Valencia, Spain
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18
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El-Moslemany RM, El-Kamel AH, Allam EA, Khalifa HM, Hussein A, Ashour AA. Tanshinone IIA loaded bioactive nanoemulsion for alleviation of lipopolysaccharide induced acute lung injury via inhibition of endothelial glycocalyx shedding. Biomed Pharmacother 2022; 155:113666. [PMID: 36099790 PMCID: PMC9466291 DOI: 10.1016/j.biopha.2022.113666] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/24/2022] [Accepted: 09/05/2022] [Indexed: 11/16/2022] Open
Abstract
Acute lung injury (ALI) and its more serious form; acute respiratory distress syndrome are major causes of COVID-19 related mortality. Finding new therapeutic targets for ALI is thus of great interest. This work aimed to prepare a biocompatible nanoformulation for effective pulmonary delivery of the herbal drug; tanshinone-IIA (TSIIA) for ALI management. A nanoemulsion (NE) formulation based on bioactive natural ingredients; rhamnolipid biosurfactant and tea-tree oil, was developed using a simple ultrasonication technique, optimized by varying oil concentration and surfactant:oil ratio. The selected TSIIA-NE formulation showed 105.7 nm diameter and a PDI ∼ 0.3. EE exceeded 98 % with biphasic sustained drug release and good stability over 3-months. In-vivo efficacy was evaluated in lipopolysaccharide (LPS)-induced ALI model. TSIIA-NE (30 µg/kg) was administered once intratracheally 2 h after LPS instillation. Evaluation was performed 7days post-treatment. Pulmonary function assessment, inflammatory, oxidative stress and glycocalyx shedding markers analysis in addition to histopathological examination of lung tissue were performed. When compared to untreated rats, in-vivo efficacy study demonstrated 1.4 and 1.9-fold increases in tidal volume and minute respiratory volume, respectively, with 32 % drop in wet/dry lung weight ratio and improved levels of arterial blood gases. Lung histopathology and biochemical analysis of different biomarkers in tissue homogenate and bronchoalveolar lavage fluid indicated that treatment may ameliorate LPS-induced ALI symptoms thorough anti-oxidative, anti-inflammatory effects and inhibition of glycocalyx degradation. TSIIA-NE efficacy was superior to free medication and blank-NE. The enhanced efficacy of TSIIA bioactive nanoemulsion significantly suggests the pharmacotherapeutic potential of bioactive TSIIA-NE as a promising nanoplatform for ALI.
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Affiliation(s)
- Riham M El-Moslemany
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
| | - Amal H El-Kamel
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
| | - Eman A Allam
- Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria 21131, Egypt
| | - Hoda M Khalifa
- Department of Histology, Faculty of Medicine, Alexandria University, Alexandria 21131, Egypt
| | - Ahmed Hussein
- Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Egypt
| | - Asmaa A Ashour
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
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19
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Joffre J, Rodriguez L, Matthay ZA, Lloyd E, Fields AT, Bainton RJ, Kurien P, Sil A, Calfee CS, Woodruff PG, Erle DJ, Hendrickson C, Krummel MF, Langelier CR, Matthay MA, Kornblith LZ, Hellman J. COVID-19-associated Lung Microvascular Endotheliopathy: A "From the Bench" Perspective. Am J Respir Crit Care Med 2022; 206:961-972. [PMID: 35649173 PMCID: PMC9801996 DOI: 10.1164/rccm.202107-1774oc] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 06/01/2022] [Indexed: 01/07/2023] Open
Abstract
Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on the lung endothelium are not well defined. We hypothesized that the lung endotheliopathy of COVID-19 is caused by circulating host factors and direct endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: We aimed to determine the effects of SARS-CoV-2 or sera from patients with COVID-19 on the permeability and inflammatory activation of lung microvascular endothelial cells. Methods: Human lung microvascular endothelial cells were treated with live SARS-CoV-2; inactivated viral particles; or sera from patients with COVID-19, patients without COVID-19, and healthy volunteers. Permeability was determined by measuring transendothelial resistance to electrical current flow, where decreased resistance signifies increased permeability. Inflammatory mediators were quantified in culture supernatants. Endothelial biomarkers were quantified in patient sera. Measurements and Main Results: Viral PCR confirmed that SARS-CoV-2 enters and replicates in endothelial cells. Live SARS-CoV-2, but not dead virus or spike protein, induces endothelial permeability and secretion of plasminogen activator inhibitor 1 and vascular endothelial growth factor. There was substantial variability in the effects of SARS-CoV-2 on endothelial cells from different donors. Sera from patients with COVID-19 induced endothelial permeability, which correlated with disease severity. Serum levels of endothelial activation and injury biomarkers were increased in patients with COVID-19 and correlated with severity of illness. Conclusions: SARS-CoV-2 infects and dysregulates endothelial cell functions. Circulating factors in patients with COVID-19 also induce endothelial cell dysfunction. Our data point to roles for both systemic factors acting on lung endothelial cells and viral infection of endothelial cells in COVID-19-associated endotheliopathy.
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Affiliation(s)
- Jérémie Joffre
- Department of Anesthesia and Perioperative Care, School of Medicine
| | - Lauren Rodriguez
- Department of Microbiology and Immunology, School of Medicine
- CoLabs
| | - Zachary A. Matthay
- Division of General Surgery, Trauma and Surgical Critical Care, Zuckerberg San Francisco General Hospital
| | - Elliot Lloyd
- Department of Anesthesia and Perioperative Care, School of Medicine
| | - Alexander T. Fields
- Division of General Surgery, Trauma and Surgical Critical Care, Zuckerberg San Francisco General Hospital
| | | | - Philip Kurien
- Department of Anesthesia and Perioperative Care, School of Medicine
| | - Anita Sil
- Department of Microbiology and Immunology, School of Medicine
| | - Carolyn S. Calfee
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine
- Cardiovascular Research Institute
| | - Prescott G. Woodruff
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine
- Cardiovascular Research Institute
- ImmunoX Initiative
| | - David J. Erle
- CoLabs
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine
- Cardiovascular Research Institute
- ImmunoX Initiative
| | - Carolyn Hendrickson
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine
- Cardiovascular Research Institute
| | | | - Charles R. Langelier
- Division of Infectious Disease, Department of Medicine, University of California, San Francisco, San Francisco, California; and
- Chan Zuckerberg Biohub, San Francisco, California
| | - Michael A. Matthay
- Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine
- Cardiovascular Research Institute
| | - Lucy Z. Kornblith
- Division of General Surgery, Trauma and Surgical Critical Care, Zuckerberg San Francisco General Hospital
| | - Judith Hellman
- Department of Anesthesia and Perioperative Care, School of Medicine
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20
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Solimando AG, Marziliano D, Ribatti D. SARS-CoV-2 and Endothelial Cells: Vascular Changes, Intussusceptive Microvascular Growth and Novel Therapeutic Windows. Biomedicines 2022; 10:2242. [PMID: 36140343 PMCID: PMC9496230 DOI: 10.3390/biomedicines10092242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/02/2022] [Accepted: 09/05/2022] [Indexed: 11/16/2022] Open
Abstract
Endothelial activation in infectious diseases plays a crucial role in understanding and predicting the outcomes and future treatments of several clinical conditions. COVID-19 is no exception. Moving from basic principles to novel approaches, an evolving view of endothelial activation provides insights into a better knowledge of the upstream actors in COVID-19 as a crucial future direction for managing SARS-CoV-2 and other infections. Assessing the function of resting and damaged endothelial cells in infection, particularly in COVID-19, five critical processes emerged controlling thrombo-resistance: vascular integrity, blood flow regulation, immune cell trafficking, angiogenesis and intussusceptive microvascular growth. Endothelial cell injury is associated with thrombosis, increased vessel contraction and a crucial phenomenon identified as intussusceptive microvascular growth, an unprecedented event of vessel splitting into two lumens through the integration of circulating pro-angiogenic cells. An essential awareness of endothelial cells and their phenotypic changes in COVID-19 inflammation is pivotal to understanding the vascular biology of infections and may offer crucial new therapeutic windows.
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Affiliation(s)
- Antonio Giovanni Solimando
- Guido Baccelli Unit of Internal Medicine, Department of Biomedical Sciences and Human Oncology, School of Medicine, Aldo Moro University of Bari, 70124 Bari, Italy
| | - Donatello Marziliano
- Guido Baccelli Unit of Internal Medicine, Department of Biomedical Sciences and Human Oncology, School of Medicine, Aldo Moro University of Bari, 70124 Bari, Italy
| | - Domenico Ribatti
- Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, University of Bari Medical School, 70124 Bari, Italy
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21
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Nishibori M. Novel aspects of sepsis pathophysiology: NETs, plasma glycoproteins, endotheliopathy and COVID-19. J Pharmacol Sci 2022; 150:9-20. [PMID: 35926948 PMCID: PMC9197787 DOI: 10.1016/j.jphs.2022.06.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 06/02/2022] [Accepted: 06/07/2022] [Indexed: 12/13/2022] Open
Abstract
In 2016, sepsis was newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis remains one of the crucial medical problems to be solved worldwide. Although the world health organization has made sepsis a global health priority, there remain no specific and effective therapy for sepsis so far. Indeed, over the previous decades almost all attempts to develop novel drugs have failed. This may be partly ascribable to the multifactorial complexity of the septic cascade and the resultant difficulties of identifying drug targets. In addition, there might still be missing links among dysregulated host responses in vital organs. In this review article, recent advances in understanding of the complex pathophysiology of sepsis are summarized, with a focus on neutrophil extracellular traps (NETs), the significant role of NETs in thrombosis/embolism, and the functional roles of plasma proteins, histidine-rich glycoprotein (HRG) and inter-alpha-inhibitor proteins (IAIPs). The specific plasma proteins that are markedly decreased in the acute phase of sepsis may play important roles in the regulation of blood cells, vascular endothelial cells and coagulation. The accumulating evidence may provide us with insights into a novel aspect of the pathophysiology of sepsis and septic ARDS, including that in COVID-19.
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Affiliation(s)
- M Nishibori
- Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
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22
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Suzuki A, Tomita H, Okada H. Form follows function: The endothelial glycocalyx. Transl Res 2022; 247:158-167. [PMID: 35421613 DOI: 10.1016/j.trsl.2022.03.014] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 03/30/2022] [Accepted: 03/31/2022] [Indexed: 10/18/2022]
Abstract
Three types of capillaries, namely continuous, fenestrated, and sinusoidal, form the microvascular system; each type has a specialized structure and function to respond to the demands of the organs they supply. The endothelial glycocalyx, a gel-like layer of glycoproteins that covers the luminal surface of the capillary endothelium, is also thought to maintain organ and vascular homeostasis by exhibiting different morphologies based on the functions of the organs and capillaries in which it is found. Recent advances in analytical technology have enabled more detailed observations of the endothelial glycocalyx, revealing that it indeed differs in structure across various organs. Furthermore, differences in the lectin staining patterns suggest the presence of different endothelial glycocalyx components across various organs. Interestingly, injury to the endothelial glycocalyx due to various pathologic and physiological stimuli causes the release of these components into the blood. Thus, circulating glycocalyx components may be useful biomarkers of organ dysfunction and disease severity. Moreover, a recent study suggested that chronic injury to the glycocalyx reduces the production of these glycocalyx components and changes their structure, leading it to become more vulnerable to external stimuli. In this review, we have summarized the various endothelial glycocalyx structures and their functions.
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Affiliation(s)
- Akio Suzuki
- Department of Pharmacy, Gifu University Hospital, Gifu, Japan
| | - Hiroyuki Tomita
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hideshi Okada
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
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23
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Li YX, Wang HB, Li J, Jin JB, Hu JB, Yang CL. Targeting pulmonary vascular endothelial cells for the treatment of respiratory diseases. Front Pharmacol 2022; 13:983816. [PMID: 36110525 PMCID: PMC9468609 DOI: 10.3389/fphar.2022.983816] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 08/08/2022] [Indexed: 11/24/2022] Open
Abstract
Pulmonary vascular endothelial cells (VECs) are the main damaged cells in the pathogenesis of various respiratory diseases and they mediate the development and regulation of the diseases. Effective intervention targeting pulmonary VECs is of great significance for the treatment of respiratory diseases. A variety of cell markers are expressed on the surface of VECs, some of which can be specifically combined with the drugs or carriers modified by corresponding ligands such as ICAM-1, PECAM-1, and P-selectin, to achieve effective delivery of drugs in lung tissues. In addition, the great endothelial surface area of the pulmonary vessels, the “first pass effect” of venous blood in lung tissues, and the high volume and relatively slow blood perfusion rate of pulmonary capillaries further promote the drug distribution in lung tissues. This review summarizes the representative markers at the onset of respiratory diseases, drug delivery systems designed to target these markers and their therapeutic effects.
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Affiliation(s)
- Yi-Xuan Li
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, China
| | - Hong-Bo Wang
- Department of Pharmacy, Yuyao People’s Hospital, Yuyao, China
| | - Jing Li
- Department of Pharmacy, Yuyao People’s Hospital, Yuyao, China
| | - Jian-Bo Jin
- Department of Pharmacy, Yuyao People’s Hospital, Yuyao, China
| | - Jing-Bo Hu
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, China
- *Correspondence: Jing-Bo Hu, ; Chun-Lin Yang,
| | - Chun-Lin Yang
- Department of Pharmacy, Yuyao People’s Hospital, Yuyao, China
- *Correspondence: Jing-Bo Hu, ; Chun-Lin Yang,
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24
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Kabedev A, Lobaskin V. Endothelial glycocalyx permeability for nanoscale solutes. Nanomedicine (Lond) 2022; 17:979-996. [PMID: 35815713 DOI: 10.2217/nnm-2021-0367] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Glycocalyx has a great impact on the accessibility of the endothelial cell membranes. Although the specific interactions play a crucial role in cross-membrane solute transport, nonspecific interactions cannot be neglected. In this work, we used computational modeling to quantify the nonspecific interactions that control the distribution of nanosized solutes across the endothelial glycocalyx. We evaluated the probabilities of various nanoparticles' passage through the luminal layer to the membrane. The calculations demonstrate that excluded volume and electrostatic interactions are decisive for the solute transport as compared with van der Waals and hydrodynamic interactions. Damaged glycocalyx models showed a relatively weak efficiency in sieving plasma solutes. We estimated the energy barriers and corresponding mean first passage times for nanoscale solute transport through the model glycocalyx.
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Affiliation(s)
- Aleksei Kabedev
- School of Physics, University College Dublin, Dublin 4, Ireland.,Department of Pharmacy, Uppsala University, Husargatan 3, Uppsala, 75 123, Sweden
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25
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Sodagar A, Javed R, Tahir H, Razak SIA, Shakir M, Naeem M, Yusof AHA, Sagadevan S, Hazafa A, Uddin J, Khan A, Al-Harrasi A. Pathological Features and Neuroinflammatory Mechanisms of SARS-CoV-2 in the Brain and Potential Therapeutic Approaches. Biomolecules 2022; 12:971. [PMID: 35883527 PMCID: PMC9313047 DOI: 10.3390/biom12070971] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/03/2022] [Accepted: 07/04/2022] [Indexed: 11/16/2022] Open
Abstract
The number of deaths has been increased due to COVID-19 infections and uncertain neurological complications associated with the central nervous system. Post-infections and neurological manifestations in neuronal tissues caused by COVID-19 are still unknown and there is a need to explore how brainstorming promoted congenital impairment, dementia, and Alzheimer's disease. SARS-CoV-2 neuro-invasion studies in vivo are still rare, despite the fact that other beta-coronaviruses have shown similar properties. Neural (olfactory or vagal) and hematogenous (crossing the blood-brain barrier) pathways have been hypothesized in light of new evidence showing the existence of SARS-CoV-2 host cell entry receptors into the specific components of human nerve and vascular tissue. Spike proteins are the primary key and structural component of the COVID-19 that promotes the infection into brain cells. Neurological manifestations and serious neurodegeneration occur through the binding of spike proteins to ACE2 receptor. The emerging evidence reported that, due to the high rate in the immediate wake of viral infection, the olfactory bulb, thalamus, and brain stem are intensely infected through a trans-synaptic transfer of the virus. It also instructs the release of chemokines, cytokines, and inflammatory signals immensely to the blood-brain barrier and infects the astrocytes, which causes neuroinflammation and neuron death; and this induction of excessive inflammation and immune response developed in more neurodegeneration complications. The present review revealed the pathophysiological effects, molecular, and cellular mechanisms of possible entry routes into the brain, pathogenicity of autoantibodies and emerging immunotherapies against COVID-19.
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Affiliation(s)
- Aisha Sodagar
- Department of Botany, Faculty of Sciences, University of Agriculture, Faisalabad 38040, Pakistan;
| | - Rasab Javed
- Institute of Microbiology, University of Agriculture, Faisalabad 38040, Pakistan;
| | - Hira Tahir
- Department of Botany, Government College Women University Faisalabad, Faisalabad 38000, Pakistan;
| | - Saiful Izwan Abd Razak
- Bioinspired Device and Tissue Engineering Research Group, School of Biomedical Engineering and Health Sciences, Faculty of Engineering, Universiti Teknologi Malaysia, Johor Bahru 81310, Johor, Malaysia;
- Sports Innovation & Technology Centre, Institute of Human Centred Engineering, Universiti Teknologi Malaysia, Johor Bahru 81310, Johor, Malaysia
| | - Muhammad Shakir
- School of Life Sciences, Northeast Normal University, Changchun 130024, China;
| | - Muhammad Naeem
- College of Life Science, Hebei Normal University, Shijiazhuang 050024, China;
| | - Abdul Halim Abdul Yusof
- School of Chemical and Energy Engineering, Faculty of Engineering, Universiti Teknologi Malaysia, Johor Bahru 81310, Johor, Malaysia;
| | - Suresh Sagadevan
- Nanotechnology & Catalysis Research Centre, University of Malaya, Kuala Lumpur 50603, Kuala Lumpur, Malaysia;
| | - Abu Hazafa
- Department of Biochemistry, Faculty of Sciences, University of Agriculture, Faisalabad 38040, Pakistan
| | - Jalal Uddin
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia;
| | - Ajmal Khan
- Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, Nizwa 616, Oman
| | - Ahmed Al-Harrasi
- Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, Nizwa 616, Oman
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26
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Tomita H, Suzuki K, Komatsu M, Okada H. Editorial: Vascular Endothelial Glycocalyx in Cardiovascular Disease. Front Cardiovasc Med 2022; 9:952022. [PMID: 35845081 PMCID: PMC9284031 DOI: 10.3389/fcvm.2022.952022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 06/03/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Hiroyuki Tomita
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
- *Correspondence: Hiroyuki Tomita /0000-0002-3291-0274
| | - Kodai Suzuki
- Department of Surgery, Columbia University, New York, NY, United States
| | - Masanobu Komatsu
- Department of Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States
- Department of Surgery, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States
| | - Hideshi Okada
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
- Hideshi Okada /0000-0002-7775-4308
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27
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Zhang J, Hui Y, Liu F, Yang Q, Lu Y, Chang Y, Liu Q, Ding Y. Neohesperidin Protects Angiotensin II-Induced Hypertension and Vascular Remodeling. Front Pharmacol 2022; 13:890202. [PMID: 35677431 PMCID: PMC9168427 DOI: 10.3389/fphar.2022.890202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 04/29/2022] [Indexed: 11/17/2022] Open
Abstract
Vascular remodeling due to hypertension is one of the major health challenges facing countries around the world. Neohesperidin, a flavonoid glycoside found in citrus fruits, is an antioxidant. Neohesperidin has been studied for a variety of diseases in addition to hypertension. In this study, angiotensin II was used to induce hypertension in mice (490 ng/kg/min, 14 days). We used H&E, Masson, immunofluorescence, dihydroethidine and qPCR to evaluate the effect of Nehesperidin (50 mg/kg/day, 16 days) on pathological hypertension in mice. Estimating the effect of Nehesperidin on human umbilical vein endothelial cells and vascular smooth muscle cells stimulated by angiotensin II. We found that neohesperidin inhibited angiotensin II-induced hypertension in mice. Neohesperidin reduced angiotensin II-induced vascular hypertrophy, fibrosis, inflammation and oxidative stress in vivo. Neohesperidin inhibited angiotensin II-induced ROS and DNA damage in human umbilical vein endothelial cells. Neohesperidin inhibited angiotensin II-induced migration of vascular smooth muscle cells. The results showed that Nehesperidin acts as an antioxidant and could significantly inhibit angiotensin II induced hypertension and vascular remodeling in vitro and in vivo.
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Affiliation(s)
- Jingsi Zhang
- Department of Cardiology II, The Second Hospital of Dalian Medical University, Dalian, China
| | - Yuanshu Hui
- Department of Heart Function Examination, The Second Hospital of Dalian Medical University, Dalian, China
| | - Fengyi Liu
- Department of Cardiology II, The Second Hospital of Dalian Medical University, Dalian, China
| | - Qian Yang
- Department of Cardiology II, The Second Hospital of Dalian Medical University, Dalian, China
| | - Yi Lu
- Department of Cardiology II, The Second Hospital of Dalian Medical University, Dalian, China
| | - Yeting Chang
- Department of Cardiology II, The Second Hospital of Dalian Medical University, Dalian, China
| | - Qinlong Liu
- Department of Hepatobiliary Pancreatic Surgery II, The Second Hospital of Dalian Medical University, Dalian, China
| | - Yanchun Ding
- Department of Cardiology II, The Second Hospital of Dalian Medical University, Dalian, China
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28
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Chen X, Qiao WH, Cao H, Shi JW, Du XL, Dong NG. Role of Neuroimmune Interactions in COVID-19-related Cardiovascular Damage. Curr Med Sci 2022; 42:555-560. [PMID: 35678914 PMCID: PMC9178934 DOI: 10.1007/s11596-022-2529-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 09/07/2021] [Indexed: 12/15/2022]
Abstract
Coronavirus disease 2019 (COVID-19) has caused a global pandemic impacting over 200 countries/regions and more than 200 million patients worldwide. Among the infected patients, there is a high prevalence of COVID-19-related cardiovascular injuries. However, the specific mechanisms linking cardiovascular damage and COVID-19 remain unclear. The COVID-19 pandemic also has exacerbated the mental health burden of humans. Considering the close association between neuroimmune interactions and cardiovascular disease, this review assessed the complex pathophysiological mechanisms connecting neuroimmune interactions and cardiovascular disease. It was revealed that the mental health burden might be a pivotal accomplice causing COVID-19-associated cardiovascular damage. Specifically, the proinflammatory status of patients with a terrible mood state is closely related to overdrive of the hypothalamus-pituitary-adrenal (HPA) axis, sympathovagal imbalance, and endothelial dysfunction, which lead to an increased risk of developing cardiovascular injury during COVID-19. Therefore, during the prevention and treatment of cardiovascular complications in COVID-19 patients, particular attention should be given to relieve the mental health burden of these patients.
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Affiliation(s)
- Xing Chen
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Wei-hua Qiao
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Hong Cao
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Jia-wei Shi
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Xin-ling Du
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
| | - Nian-guo Dong
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
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29
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Li Y, Lu H, Sun Y. Correlation of NO and ET-1 Levels with Blood Pressure Changes in Hemodialysis Patients after Arteriovenous Fistula Surgery. Front Surg 2022; 9:905372. [PMID: 35651688 PMCID: PMC9149304 DOI: 10.3389/fsurg.2022.905372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 04/15/2022] [Indexed: 11/13/2022] Open
Abstract
Hemodialysis (HD) is the most common renal replacement therapy for patients with end-stage renal disease (ESRD) and can significantly reduce mortality and improve the quality of life of patients. The occurrence of intradialytic hypotension and intradialytic hypertension are important risk factors for death and disability during dialysis in patients with ESRD, yet their etiology remains unclear, and some studies suggest that nitric oxide (NO) and endothelin-1 (ET-1) may play an important role in these hemodynamic alterations. For this purpose we examined the changes in NO and ET-1 levels during hemodialysis in 30 patients on maintenance hemodialysis (MHD) after arteriovenous fistula surgery. Thirty dialysis patients were divided into group I (stable blood pressure during dialysis), group II (Intradialytic hypotension) and group III (Intradialytic hypertension) according to the change of blood pressure (BP) during hemodialysis, with 10 cases in each group. BP of MHD patients were measured Pre-dialysis (Pre-D), at 1 h of dialysis (1h-D), at 2 h of dialysis (Mid-D, 2h-D), at 3 h of dialysis (3h-D), and at the end of dialysis (Post-D); and blood samples were taken from the arterial end at Pre-D, Mid-D, and Post-D to measure NO and ET-1 levels. The results of the analysis showed that as dialysis proceeded and ended, the NO levels in the three groups gradually decreased, with significant differences compared with those before dialysis (p < 0.05); the ET-1 levels in group III gradually increased, with significant differences compared with those before dialysis (p < 0.05), while the increasing trend of ET-1 levels in group I and group II was not significant. The increasing trend of MAP in group I was not significant (p > 0.05); MAP in group II showed a gradual decrease and MAP in group III showed an increasing trend, and the difference between MAP after dialysis and before dialysis was significant (p < 0.05). Correlation analysis showed a significant positive correlation between ET-1 levels and MAP in Group III at Mid-D (r = 0.847, p = 0.002). This shows that serum ET-1 and NO levels are significantly higher than normal in MHD patients after arteriovenous endovascular fistula surgery, and both ET-1 and NO levels are changing during dialysis, and there may be a link between their changes and blood pressure changes. It is suggested that the blood pressure fluctuations that occur during dialysis in MHD patients may be related to endothelial cell dysfunction.
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Maldonado F, Morales D, Díaz-Papapietro C, Valdés C, Fernandez C, Valls N, Lazo M, Espinoza C, González R, Gutiérrez R, Jara Á, Romero C, Cerda O, Cáceres M. Relationship Between Endothelial and Angiogenesis Biomarkers Envisage Mortality in a Prospective Cohort of COVID-19 Patients Requiring Respiratory Support. Front Med (Lausanne) 2022; 9:826218. [PMID: 35372407 PMCID: PMC8966493 DOI: 10.3389/fmed.2022.826218] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 02/18/2022] [Indexed: 12/15/2022] Open
Abstract
Purpose Endothelial damage and angiogenesis are fundamental elements of neovascularisation and fibrosis observed in patients with coronavirus disease 2019 (COVID-19). Here, we aimed to evaluate whether early endothelial and angiogenic biomarkers detection predicts mortality and major cardiovascular events in patients with COVID-19 requiring respiratory support. Methods Changes in serum syndecan-1, thrombomodulin, and angiogenic factor concentrations were analysed during the first 24 h and 10 days after COVID-19 hospitalisation in patients with high-flow nasal oxygen or mechanical ventilation. Also, we performed an exploratory evaluation of the endothelial migration process induced by COVID-19 in the patients' serum using an endothelial cell culture model. Results In 43 patients, mean syndecan-1 concentration was 40.96 ± 106.9 ng/mL with a 33.9% increase (49.96 ± 58.1 ng/mL) at day 10. Both increases were significant compared to healthy controls (Kruskal–Wallis p < 0.0001). We observed an increase in thrombomodulin, Angiopoietin-2, human vascular endothelial growth factor (VEGF), and human hepatocyte growth factor (HGF) concentrations during the first 24 h, with a decrease in human tissue inhibitor of metalloproteinases-2 (TIMP-2) that remained after 10 days. An increase in human Interleukin-8 (IL-8) on the 10th day accompanied by high HGF was also noted. The incidence of myocardial injury and pulmonary thromboembolism was 55.8 and 20%, respectively. The incidence of in-hospital deaths was 16.3%. Biomarkers showed differences in severity of COVID-19. Syndecan-1, human platelet-derived growth factor (PDGF), VEGF, and Ang-2 predicted mortality. A multiple logistic regression model with TIMP-2 and PDGF had positive and negative predictive powers of 80.9 and 70%, respectively, for mortality. None of the biomarkers predicted myocardial injury or pulmonary thromboembolism. A proteome profiler array found changes in concentration in a large number of biomarkers of angiogenesis and chemoattractants. Finally, the serum samples from COVID-19 patients increased cell migration compared to that from healthy individuals. Conclusion We observed that early endothelial and angiogenic biomarkers predicted mortality in patients with COVID-19. Chemoattractants from patients with COVID-19 increase the migration of endothelial cells. Trials are needed for confirmation, as this poses a therapeutic target for SARS-CoV-2.
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Affiliation(s)
- Felipe Maldonado
- Department of Anaesthesia and Perioperative Medicine, Faculty of Medicine, Hospital Clínico de la Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Diego Morales
- Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Catalina Díaz-Papapietro
- Department of Anaesthesia and Perioperative Medicine, Faculty of Medicine, Hospital Clínico de la Universidad de Chile, Universidad de Chile, Santiago, Chile.,Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Catalina Valdés
- Department of Anaesthesia and Perioperative Medicine, Faculty of Medicine, Hospital Clínico de la Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Christian Fernandez
- Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago, Chile
| | - Nicolas Valls
- Department of Anaesthesia and Perioperative Medicine, Faculty of Medicine, Hospital Clínico de la Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Marioli Lazo
- Critical Care Unit, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Carolina Espinoza
- Emergency Department, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Roberto González
- Department of Anaesthesia and Perioperative Medicine, Faculty of Medicine, Hospital Clínico de la Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Rodrigo Gutiérrez
- Department of Anaesthesia and Perioperative Medicine, Faculty of Medicine, Hospital Clínico de la Universidad de Chile, Universidad de Chile, Santiago, Chile.,Centro de Investigación Clínica Avanzada, Faculty of Medicine, Hospital Clínico de la Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Álvaro Jara
- Department of Anaesthesia and Perioperative Medicine, Faculty of Medicine, Hospital Clínico de la Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Carlos Romero
- Critical Care Unit, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Oscar Cerda
- Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago, Chile.,Millennium Nucleus of Ion Channel-Associated Diseases, Santiago, Chile
| | - Mónica Cáceres
- Program of Cellular and Molecular Biology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago, Chile.,Millennium Nucleus of Ion Channel-Associated Diseases, Santiago, Chile.,Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
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Effect of Sulodexide on Circulating Blood Cells in Patients with Mild COVID-19. J Clin Med 2022; 11:jcm11071995. [PMID: 35407602 PMCID: PMC8999543 DOI: 10.3390/jcm11071995] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/20/2022] [Accepted: 03/30/2022] [Indexed: 02/01/2023] Open
Abstract
Background. Despite the fact that COVID-19 usually manifests with severe pneumonia, there is a growing body of evidence that life-threatening multiorgan damage is caused by vascular and hemostatic abnormalities. Since there is no established therapy, assessing antithrombotics is indeed important. Sulodexide, a compound derived from porcine intestinal mucosa is a mixture of fast-moving heparin fraction (80%) and dermatan sulfate (20%), is approved in Europe and currently in trials for COVID-19 indication. Methods. This single-center, prospective, observational study included 28 patients with mild COVID-19 hospitalized in the Central Clinical Hospital of the Presidential Administration of the Russian Federation. Patients in the control group (n = 14) were treated using routine therapy according to current guidelines, while patients in the experimental group (n = 14) had the routine treatment supplemented with daily intravenous injections of sulodexide in 600-unit doses. Scanning electron microscopy was utilized to examine the blood specimens derived from the cubital vein at admission and at 10 days after hospitalization, which was approximately the average duration of patients’ treatment in the hospital (11.6 ± 0.4 days). Results. Sulodexide significantly (by 40%) diminished the score of circulating endothelial cells, potentially indicating its antiviral endothelium-protective properties. It also prevented the extra activation of the platelets and the formation of erythrocytic sludges. Among patients in the control group, the share of activated platelets rose from 37 ± 5% to 45 ± 6% (p = 0.04) over the course of the study period, whereas among patients in the experimental group, the share of activated platelets remained practically unchanged (43 ± 6% vs. 38 ± 4%, p = 0.22). The score of erythrocytic sludges in the control group remained practically the same (4.8 ± 1.1 at admission vs. 3.9 ± 0.9 after 10 days, p = 0.67), whereas in the experimental group, it significantly decreased (from 5.7 ± 1.7 to 2.4 ± 0.9, p = 0.03). Conclusions. Sulodexide is able to defend endothelium, normalize blood, and, seemingly, prevent thrombosis. Therefore, it may be considered as a promising and effective agent for the treatment of patients with mild COVID-19. Broader randomized trials are needed to assess whether the observed findings will transform into sustained long-term clinical benefit.
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Astapenko D, Tomasova A, Ticha A, Hyspler R, Chua HS, Manzoor M, Skulec R, Lehmann C, Hahn R, Malbrain ML, Cerny V. Endothelial glycocalyx damage in patients with severe COVID-19 on mechanical ventilation - a prospective observational pilot study. Clin Hemorheol Microcirc 2022; 81:205-219. [PMID: 35342082 DOI: 10.3233/ch-221401] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Coronavirus disease (COVID-19) associated endotheliopathy and microvascular dysfunction are of concern. OBJECTIVE The objective of the present single-center observational pilot study was to compare endothelial glycocalyx (EG) damage and endotheliopathy in patients with severe COVID-19 (COVID-19 group) with patients with bacterial pneumonia with septic shock (non-COVID group). METHODS Biomarkers of EG damage (syndecan-1), endothelial cells (EC) damage (thrombomodulin), and activation (P-selectin) were measured in blood on three consecutive days from admission to the intensive care unit (ICU). The sublingual microcirculation was studied by Side-stream Dark Field (SDF) imaging with automatic assessment. RESULTS We enrolled 13 patients in the non-COVID group (mean age 70 years, 6 women), and 15 in the COVID-19 group (64 years old, 3 women). The plasma concentrations of syndecan-1 were significantly higher in the COVID-19 group during all three days. Differences regarding other biomarkers were not statistically significant. The assessment of the sublingual microcirculation showed improvement on Day 2 in the COVID-19 group. Plasma levels of C-reactive protein (CRP) were significantly higher on the first two days in the COVID-19 group. Plasma syndecan-1 and CRP were higher in patients suffering from severe COVID-19 pneumonia compared to bacterial pneumonia patients. CONCLUSIONS These findings support the role of EG injury in the microvascular dysfunction in COVID-19 patients who require ICU.
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Affiliation(s)
- David Astapenko
- Department of Anesthesiology, Resuscitation and Intensive Care Medicine, University Hospital Hradec Kralove, Czech Republic.,Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic.,Center for Research and Development, University Hospital Hradec Kralove, Czech Republic
| | - Adela Tomasova
- Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic.,Department of Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Czech Republic
| | - Alena Ticha
- Department of Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Czech Republic
| | - Radomir Hyspler
- Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic.,Department of Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Czech Republic
| | - Huey Shin Chua
- Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
| | - Mubashar Manzoor
- Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic
| | - Roman Skulec
- Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic.,Department of Anesthesiology, Perioperative Medicine, and Intensive Care, J.E. Purkinje University, Masaryk Hospital, Usti nad Labem, Czech Republic
| | - Christian Lehmann
- Department of Anaesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada.,Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.,Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.,Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada
| | - Robert Hahn
- Research Unit, Södertälje Hospital, Sweden.,Karolinska Institutet at Danderyds Hospital (KIDS), Stockholm, Sweden
| | - Manu Lng Malbrain
- Department of Medical, Medical Direction, AZ Jan Palfijn Hospital, Gent, Belgium.,First Department of Anaesthesia and IntensiveTherapy, Medical University of Lublin, Lublin, Poland.,International Fluid Academy, Lovenjoel, Belgium
| | - Vladimir Cerny
- Department of Anesthesiology, Resuscitation and Intensive Care Medicine, University Hospital Hradec Kralove, Czech Republic.,Faculty of Medicine in Hradec Kralove, Charles University, Czech Republic.,Center for Research and Development, University Hospital Hradec Kralove, Czech Republic.,Department of Anesthesiology, Perioperative Medicine, and Intensive Care, J.E. Purkinje University, Masaryk Hospital, Usti nad Labem, Czech Republic.,Department of Anaesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada
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Keshvani N, Mehta A, Alger HM, Rutan C, Williams J, Zhang S, Young R, Alhanti B, Chiswell K, Greene SJ, DeVore AD, Yancy CW, Fonarow GC, Pandey A. Heart Failure Quality of Care and In-Hospital Outcomes During the COVID-19 Pandemic Findings from the Get With The Guidelines-Heart Failure Registry. Eur J Heart Fail 2022; 24:1117-1128. [PMID: 35289038 PMCID: PMC9087396 DOI: 10.1002/ejhf.2484] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 03/07/2022] [Accepted: 03/10/2022] [Indexed: 11/08/2022] Open
Abstract
Aims To assess heart failure (HF) in‐hospital quality of care and outcomes before and during the COVID‐19 pandemic. Methods and results Patients hospitalized for HF with ejection fraction (EF) <40% in the American Heart Association Get With The Guidelines©‐HF (GWTG‐HF) registry during the COVID‐19 pandemic (3/1/2020–4/1/2021) and pre‐pandemic (2/1/2019–2/29/2020) periods were included. Adherence to HF process of care measures, in‐hospital mortality, and length of stay (LOS) were compared in pre‐pandemic vs. pandemic periods and in patients with vs. without COVID‐19. Overall, 42 004 pre‐pandemic and 37 027 pandemic period patients (median age 68, 33% women, 58% White) were included without observed differences across clinical characteristics, comorbidities, vital signs, or EF. Utilization of guideline‐directed medical therapy at discharge was comparable across both periods, with rates of implantable cardioverter defibrillator (ICD) placement or prescription lower during the pandemic (vs. pre‐pandemic period). In‐hospital mortality (3.0% vs. 2.5%, p <0.0001) and LOS (mean 5.7 vs. 5.4 days, p <0.0004) were higher during the pandemic vs. pre‐pandemic. The highest in‐hospital mortality during the pandemic was observed among patients hospitalized in the Northeast region (3.4%). Among patients concurrently diagnosed with COVID‐19 (n = 549; 1.5%), adherence to ICD placement or prescription, prescription of aldosterone antagonist or angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor at discharge were lower, and in‐hospital mortality (8.2% vs. 3.0%, p <0.0001) and LOS (mean 7.7 vs. 5.7 days, p <0.0001) were higher than those without COVID‐19. Conclusion Among GWTG‐HF participating hospitals, patients hospitalized for HF with reduced EF during the pandemic received similar care quality but experienced higher in‐hospital mortality than the pre‐pandemic period.
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Affiliation(s)
- Neil Keshvani
- Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
| | - Anurag Mehta
- Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA
| | | | | | | | | | | | | | | | - Stephen J Greene
- Duke Clinical Research Institute, Durham, NC.,Division of Cardiology, Duke University School of Medicine, Durham, NC
| | - Adam D DeVore
- Duke Clinical Research Institute, Durham, NC.,Division of Cardiology, Duke University School of Medicine, Durham, NC
| | - Clyde W Yancy
- Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, IL
| | - Gregg C Fonarow
- Ahmanson-UCLA Cardiomyopathy Center, University of California, Los Angeles, Los Angeles, CA
| | - Ambarish Pandey
- Division of Cardiology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
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Tarnawski AS, Ahluwalia A. Endothelial cells and blood vessels are major targets for COVID-19-induced tissue injury and spreading to various organs. World J Gastroenterol 2022; 28:275-289. [PMID: 35110950 PMCID: PMC8771611 DOI: 10.3748/wjg.v28.i3.275] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 12/02/2021] [Accepted: 01/11/2022] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) infected so far over 250 million people and caused the death of over 5 million worldwide. Aging, diabetes, and cardiovascular diseases, conditions with preexisting impaired endothelial functions predispose to COVID-19. While respiratory epithelium is the main route of virus entry, the endothelial cells (ECs) lining pulmonary blood vessels are also an integral part of lung injury in COVID-19 patients. COVID-19 not only affects the lungs and respiratory system but also gastrointestinal (GI) tract, liver, pancreas, kidneys, heart, brain, and skin. Blood vessels are likely conduits for the virus dissemination to these distant organs. Importantly, ECs are also critical for vascular regeneration during injury/lesions healing and restoration of vascular network. The World Journal of Gastroenterology has published in last two years over 67 outstanding papers on COVID-19 infection with a focus on the GI tract, liver, pancreas, etc., however, the role of the endothelial and vascular components as major targets for COVID-19-induced tissue injury, spreading to various organs, and injury healing have not been sufficiently emphasized. In the present article, we focus on these subjects and on current treatments including the most recent oral drugs molnupiravir and paxlovid that show a dramatic, significant efficacy in controlling severe COVID-19 infection.
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Affiliation(s)
- Andrzej S Tarnawski
- Gastroenterology Research Department, University of California Irvine and the Veterans Administration Long Beach Healthcare System, Long Beach, CA 90822, United States
| | - Amrita Ahluwalia
- Research Service, Veterans Administration Long Beach Healthcare System, Long Beach, CA 90822, United States
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35
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Association between plasma glycocalyx component levels and poor prognosis in severe influenza type A (H1N1). Sci Rep 2022; 12:163. [PMID: 34997090 PMCID: PMC8741814 DOI: 10.1038/s41598-021-04146-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 11/29/2021] [Indexed: 11/08/2022] Open
Abstract
Influenza A virus infection causes a series of diseases, but the factors associated with disease severity are not fully understood. Disruption of the endothelial glycocalyx contributes to acute lung injury in sepsis, but has not been well studied in H1N1 influenza. We aim to determine whether the plasma glycocalyx components levels are predictive of disease severity in H1N1 influenza. This prospective observational study included 53 patients with influenza A (H1N1) during the influenza season, and 30 healthy controls in our hospital. Patients were grouped by severity and survival. We collected clinical data and blood samples at admission. Inflammatory factors (tumor necrosis factor-α, interleukin-6, interleukin-10) and endothelial glycocalyx components (syndecan-1, hyaluronan, heparan sulfate) were measured. The plasma levels of syndecan-1, hyaluronan, and heparan sulfate were significantly higher in patients with severe influenza A (H1N1) than in mild cases. Syndecan-1 and hyaluronan were positively correlated with disease severity, which was indicated by the APACHE II and SOFA scores and lactate levels, and negatively correlated with albumin levels. At a cutoff point ≥ 173.9 ng/mL, syndecan-1 had a 81.3% sensitivity and 70.3% specificity for predicting of 28-day mortality. Kaplan–Meier analysis demonstrated a strong association between syndecan-1 levels and 28-day mortality (log-rank 11.04, P = 0.001). Elevated plasma levels of syndecan-1 has a potential role in systemic organ dysfunction and may be indicative of disease severity in patients with influenza A (H1N1).
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Kusuzawa K, Suzuki K, Okada H, Suzuki K, Takada C, Nagaya S, Yasuda R, Okamoto H, Ishihara T, Tomita H, Kawasaki Y, Minamiyama T, Nishio A, Fukuda H, Shimada T, Tamaoki Y, Yoshida T, Nakashima Y, Chiba N, Yoshimura G, Kamidani R, Miura T, Oiwa H, Yamaji F, Mizuno Y, Miyake T, Kitagawa Y, Fukuta T, Doi T, Suzuki A, Yoshida T, Tetsuka N, Yoshida S, Ogura S. Measuring the Concentration of Serum Syndecan-1 to Assess Vascular Endothelial Glycocalyx Injury During Hemodialysis. Front Med (Lausanne) 2021; 8:791309. [PMID: 35004758 PMCID: PMC8733596 DOI: 10.3389/fmed.2021.791309] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 12/07/2021] [Indexed: 11/13/2022] Open
Abstract
Glycocalyx is present on the surface of healthy endothelium, and the concentration of serum syndecan-1 can serve as an injury marker. This study aimed to assess endothelial injury using serum syndecan-1 as a marker of endothelial glycocalyx injury in patients who underwent hemodialysis. In this single-center, retrospective, observational study, 145 patients who underwent hemodialysis at the Gifu University Hospital between March 2017 and December 2019 were enrolled. The median dialysis period and time were 63 months and 3.7 h, respectively. The serum syndecan-1 concentration significantly increased from 124.6 ± 107.8 ng/ml before hemodialysis to 229.0 ± 138.1 ng/ml after hemodialysis (P < 0.001). Treatment with anticoagulant nafamostat mesylate inhibited hemodialysis-induced increase in the levels of serum syndecan-1 in comparison to unfractionated heparin. Dialysis time and the change in the syndecan-1 concentration were positively correlated. Conversely, the amount of body fluid removed and the changes in the syndecan-1 concentration were not significantly correlated. The reduction in the amount of body fluid removed and dialysis time inhibited the change in the syndecan-1 levels before and after hemodialysis. In conclusion, quantitative assessment of the endothelial glycocalyx injury during hemodialysis can be performed by measuring the serum syndecan-1 concentration, which may aid in the selection of appropriate anticoagulants, reduction of hemodialysis time, and the amount of body fluid removed.
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Affiliation(s)
- Keigo Kusuzawa
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Keiko Suzuki
- Department of Infection Control, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hideshi Okada
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
- *Correspondence: Hideshi Okada
| | - Kodai Suzuki
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Chihiro Takada
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Soichiro Nagaya
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Ryu Yasuda
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Haruka Okamoto
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Takuma Ishihara
- Innovative and Clinical Research Promotion Center, Gifu University Hospital, Gifu, Japan
| | - Hiroyuki Tomita
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yuki Kawasaki
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Toru Minamiyama
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Ayane Nishio
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hirotsugu Fukuda
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Takuto Shimada
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yuto Tamaoki
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Tomoki Yoshida
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yusuke Nakashima
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Naokazu Chiba
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Genki Yoshimura
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Ryo Kamidani
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Tomotaka Miura
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
- Department of Infection Control, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Hideaki Oiwa
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
- Abuse Prevention Center, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Fuminori Yamaji
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yosuke Mizuno
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Takahito Miyake
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Yuichiro Kitagawa
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Tetsuya Fukuta
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Tomoaki Doi
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Akio Suzuki
- Department of Pharmacy, Gifu University Hospital, Gifu, Japan
| | - Takahiro Yoshida
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Nobuyuki Tetsuka
- Department of Infection Control, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Shozo Yoshida
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
- Abuse Prevention Center, Gifu University Graduate School of Medicine, Gifu, Japan
| | - Shinji Ogura
- Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
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Sampei S, Okada H, Tomita H, Suzuki A, Nawa T, Ogura S. Point of tangency between coronavirus disease and endothelial injury. Int J Emerg Med 2021; 14:76. [PMID: 34930108 PMCID: PMC8685491 DOI: 10.1186/s12245-021-00403-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 12/12/2021] [Indexed: 11/10/2022] Open
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Liang QQ, Liu L. Application of vascular endothelial cells in stem cell medicine. World J Clin Cases 2021; 9:10765-10780. [PMID: 35047589 PMCID: PMC8678855 DOI: 10.12998/wjcc.v9.i35.10765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/02/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023] Open
Abstract
Stem cell medicine is gaining momentum in the development of therapy for various end-stage diseases. The search for new seed cells and exploration of their application prospects are topics of interest in stem cell medicine. In recent years, vascular endothelial cells (VECs) have attracted wide attention from scholars. VECs, which form the inner lining of blood vessels, are critically involved in many physiological functions, including permeability, angiogenesis, blood pressure regulation, immunity, and pathological development, such as atherosclerosis and malignant tumors. VECs have significant therapeutic effects and broad application prospects in stem cell medicine for the treatment of various refractory diseases, including atherosclerosis, myocardial infarction, diabetic complications, hypertension, coronavirus disease 2019, and malignant tumors. On the one hand, VECs and their extracellular vesicles can be directly used for the treatment of these diseases. On the other hand, VECs can be used as therapeutic targets for some diseases. However, there are still some obstacles to the use of VECs in stem cell medicine. In this review, advances in the applications and challenges that come with the use of these cells are discussed.
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Affiliation(s)
- Qing-Qing Liang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lei Liu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
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Tiboldi A, Führer J, Schaubmayr W, Hunyadi-Gulyas E, Zach ML, Hochreiter B, Spittler A, Ullrich R, Markstaller K, Altmann F, Klein KU, Tretter V. Oxygen-Dependent Changes in the N-Glycome of Murine Pulmonary Endothelial Cells. Antioxidants (Basel) 2021; 10:1947. [PMID: 34943050 PMCID: PMC8750181 DOI: 10.3390/antiox10121947] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 12/02/2021] [Accepted: 12/03/2021] [Indexed: 11/21/2022] Open
Abstract
Supplemental oxygen is frequently used together with mechanical ventilation to achieve sufficient blood oxygenation. Despite the undoubted benefits, it is vigorously debated whether too much oxygen can also have unpredicted side-effects. Uncertainty is also due to the fact that the molecular mechanisms are still insufficiently understood. The lung endothelium is covered with an exceptionally broad glycocalyx, carrying N- and O-glycans, proteoglycans, glycolipids and glycosaminoglycans. Glycan structures are not genetically determined but depend on the metabolic state and the expression level and activity of biosynthetic and glycan remodeling enzymes, which can be influenced by oxygen and the redox status of the cell. Altered glycan structures can affect cell interactions and signaling. In this study, we investigated the effect of different oxygen conditions on aspects of the glycobiology of the pulmonary endothelium with an emphasis on N-glycans and terminal sialylation using an in vitro cell culture system. We combined a proteomic approach with N-glycan structure analysis by LC-MS, qRT-PCR, sialic acid analysis and lectin binding to show that constant and intermittent hyperoxia induced time dependent changes in global and surface glycosylation. An siRNA approach identified St6gal1 as being primarily responsible for the early transient increase of α2-6 sialylated structures in response to hyperoxia.
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Affiliation(s)
- Akos Tiboldi
- Department of Anesthesia, General Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria; (A.T.); (W.S.); (M.L.Z.); (B.H.); (R.U.); (K.M.); (K.U.K.)
| | - Johannes Führer
- Division of Biochemistry, Department of Chemistry, University of Natural Resources and Life Sciences, 1090 Vienna, Austria; (J.F.); (F.A.)
| | - Wolfgang Schaubmayr
- Department of Anesthesia, General Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria; (A.T.); (W.S.); (M.L.Z.); (B.H.); (R.U.); (K.M.); (K.U.K.)
| | - Eva Hunyadi-Gulyas
- Laboratory of Proteomics Research, Biological Research Centre, 6726 Szeged, Hungary;
| | - Marie Louise Zach
- Department of Anesthesia, General Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria; (A.T.); (W.S.); (M.L.Z.); (B.H.); (R.U.); (K.M.); (K.U.K.)
| | - Beatrix Hochreiter
- Department of Anesthesia, General Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria; (A.T.); (W.S.); (M.L.Z.); (B.H.); (R.U.); (K.M.); (K.U.K.)
| | - Andreas Spittler
- Department of Surgery and Core Facility Flow Cytometry, Medical University Vienna, 1090 Vienna, Austria;
| | - Roman Ullrich
- Department of Anesthesia, General Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria; (A.T.); (W.S.); (M.L.Z.); (B.H.); (R.U.); (K.M.); (K.U.K.)
| | - Klaus Markstaller
- Department of Anesthesia, General Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria; (A.T.); (W.S.); (M.L.Z.); (B.H.); (R.U.); (K.M.); (K.U.K.)
| | - Friedrich Altmann
- Division of Biochemistry, Department of Chemistry, University of Natural Resources and Life Sciences, 1090 Vienna, Austria; (J.F.); (F.A.)
| | - Klaus Ulrich Klein
- Department of Anesthesia, General Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria; (A.T.); (W.S.); (M.L.Z.); (B.H.); (R.U.); (K.M.); (K.U.K.)
| | - Verena Tretter
- Department of Anesthesia, General Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria; (A.T.); (W.S.); (M.L.Z.); (B.H.); (R.U.); (K.M.); (K.U.K.)
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Indications of Persistent Glycocalyx Damage in Convalescent COVID-19 Patients: A Prospective Multicenter Study and Hypothesis. Viruses 2021; 13:v13112324. [PMID: 34835130 PMCID: PMC8619155 DOI: 10.3390/v13112324] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/24/2021] [Accepted: 11/19/2021] [Indexed: 12/18/2022] Open
Abstract
The COVID-19 pandemic is caused by the SARS CoV-2 virus and can lead to severe lung damage and hyperinflammation. In the context of COVID-19 infection, inflammation-induced degradation of the glycocalyx layer in endothelial cells has been demonstrated. Syndecan-1 (SDC-1) is an established parameter for measuring glycocalyx injury. This prospective, multicenter, observational, cross-sectional study analyzed SDC-1 levels in 24 convalescent patients that had been infected with SARS-CoV-2 with mild disease course without need of hospitalization. We included 13 age-matched healthy individuals and 10 age-matched hospitalized COVID-19 patients with acute mild disease course as controls. In convalescent COVID-19 patients, significantly elevated SDC-1 levels were detected after a median of 88 days after symptom onset compared to healthy controls, whereas no difference was found when compared to SDC-1 levels of hospitalized patients undergoing acute disease. This study is the first to demonstrate signs of endothelial damage in non-pre-diseased, convalescent COVID-19 patients after mild disease progression without hospitalization. The data are consistent with studies showing evidence of persistent endothelial damage after severe or critical disease progression. Further work to investigate endothelial damage in convalescent COVID-19 patients should follow.
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Cumpstey AF, Clark AD, Santolini J, Jackson AA, Feelisch M. COVID-19: A Redox Disease-What a Stress Pandemic Can Teach Us About Resilience and What We May Learn from the Reactive Species Interactome About Its Treatment. Antioxid Redox Signal 2021; 35:1226-1268. [PMID: 33985343 DOI: 10.1089/ars.2021.0017] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Significance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19), affects every aspect of human life by challenging bodily, socioeconomic, and political systems at unprecedented levels. As vaccines become available, their distribution, safety, and efficacy against emerging variants remain uncertain, and specific treatments are lacking. Recent Advances: Initially affecting the lungs, COVID-19 is a complex multisystems disease that disturbs the whole-body redox balance and can be long-lasting (Long-COVID). Numerous risk factors have been identified, but the reasons for variations in susceptibility to infection, disease severity, and outcome are poorly understood. The reactive species interactome (RSI) was recently introduced as a framework to conceptualize how cells and whole organisms sense, integrate, and accommodate stress. Critical Issues: We here consider COVID-19 as a redox disease, offering a holistic perspective of its effects on the human body, considering the vulnerability of complex interconnected systems with multiorgan/multilevel interdependencies. Host/viral glycan interactions underpin SARS-CoV-2's extraordinary efficiency in gaining cellular access, crossing the epithelial/endothelial barrier to spread along the vascular/lymphatic endothelium, and evading antiviral/antioxidant defences. An inflammation-driven "oxidative storm" alters the redox landscape, eliciting epithelial, endothelial, mitochondrial, metabolic, and immune dysfunction, and coagulopathy. Concomitantly reduced nitric oxide availability renders the sulfur-based redox circuitry vulnerable to oxidation, with eventual catastrophic failure in redox communication/regulation. Host nutrient limitations are crucial determinants of resilience at the individual and population level. Future Directions: While inflicting considerable damage to health and well-being, COVID-19 may provide the ultimate testing ground to improve the diagnosis and treatment of redox-related stress diseases. "Redox phenotyping" of patients to characterize whole-body RSI status as the disease progresses may inform new therapeutic approaches to regain redox balance, reduce mortality in COVID-19 and other redox diseases, and provide opportunities to tackle Long-COVID. Antioxid. Redox Signal. 35, 1226-1268.
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Affiliation(s)
- Andrew F Cumpstey
- Respiratory and Critical Care Research Group, Southampton NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.,Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Anna D Clark
- Respiratory and Critical Care Research Group, Southampton NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.,Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Jérôme Santolini
- Institute for Integrative Biology of the Cell (I2BC), Biochemistry, Biophysics and Structural Biology, CEA, CNRS, Université Paris-Sud, Universite Paris-Saclay, Gif-sur-Yvette, France
| | - Alan A Jackson
- Human Nutrition, University of Southampton and University Hospital Southampton, Southampton, United Kingdom
| | - Martin Feelisch
- Respiratory and Critical Care Research Group, Southampton NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.,Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
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Ai J, Hong W, Wu M, Wei X. Pulmonary vascular system: A vulnerable target for COVID-19. MedComm (Beijing) 2021; 2:531-547. [PMID: 34909758 PMCID: PMC8662299 DOI: 10.1002/mco2.94] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/18/2021] [Accepted: 09/21/2021] [Indexed: 02/05/2023] Open
Abstract
The number of coronavirus disease 2019 (COVID‐19) cases has been increasing significantly, and the disease has evolved into a global pandemic, posing an unprecedented challenge to the healthcare community. Angiotensin‐converting enzyme 2, the binding and entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in hosts, is also expressed on pulmonary vascular endothelium; thus, pulmonary vasculature is a potential target in COVID‐19. Indeed, pulmonary vascular thickening is observed by early clinical imaging, implying a tropism of SARS‐CoV‐2 for pulmonary vasculature. Recent studies reported that COVID‐19 is associated with vascular endothelial damage and dysfunction along with inflammation, coagulopathy, and microthrombosis; all of these pathologic changes are the hallmarks of pulmonary vascular diseases. Notwithstanding the not fully elucidated effects of COVID‐19 on pulmonary vasculature, the vascular endotheliopathy that occurs after infection is attributed to direct infection and indirect damage mainly caused by renin‐angiotensin‐aldosterone system imbalance, coagulation cascade, oxidative stress, immune dysregulation, and intussusceptive angiogenesis. Degradation of endothelial glycocalyx exposes endothelial cell (EC) surface receptors to the vascular lumen, which renders pulmonary ECs more susceptible to SARS‐CoV‐2 infection. The present article reviews the potential pulmonary vascular pathophysiology and clinical presentations in COVID‐19 to provide a basis for clinicians and scientists, providing insights into the development of therapeutic strategies targeting pulmonary vasculature.
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Affiliation(s)
- Jiayuan Ai
- Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy National Clinical Research Center for Geriatrics West China Hospital Sichuan University Chengdu Sichuan PR China
| | - Weiqi Hong
- Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy National Clinical Research Center for Geriatrics West China Hospital Sichuan University Chengdu Sichuan PR China
| | - Min Wu
- Department of Biomedical Sciences School of Medicine and Health Sciences University of North Dakota Grand Forks North Dakota USA
| | - Xiawei Wei
- Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy National Clinical Research Center for Geriatrics West China Hospital Sichuan University Chengdu Sichuan PR China
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Yang YY, Chen Z, Yang XD, Deng RR, Shi LX, Yao LY, Xiang DX. Piperazine ferulate prevents high-glucose-induced filtration barrier injury of glomerular endothelial cells. Exp Ther Med 2021; 22:1175. [PMID: 34504620 PMCID: PMC8393711 DOI: 10.3892/etm.2021.10607] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 07/19/2021] [Indexed: 12/14/2022] Open
Abstract
Filtration barrier injury induced by high glucose (HG) levels leads to the development of diabetic nephropathy. The endothelial glycocalyx plays a critical role in glomerular barrier function. In the present study, the effects of piperazine ferulate (PF) on HG-induced filtration barrier injury of glomerular endothelial cells (GEnCs) were investigated and the underlying mechanism was assessed. Immunofluorescence was used to observe the distribution of the glycocalyx as well as the expression levels of syndecan-1 and Zonula occludens-1 (ZO-1). Endothelial permeability assays were performed to assess the effects of PF on the integrity of the filtration barrier. Protein and mRNA expression levels were measured by western blotting and reverse transcription-quantitative PCR analyses, respectively. In vitro experiments revealed that adenosine monophosphate-activated protein kinase (AMPK) mediated HG-induced glycocalyx degradation and endothelial barrier injury. PF inhibited the HG-induced endothelial barrier injury and restored the expression levels of heparanase-1 (Hpa-1), ZO-1 and occludin-1 by AMPK. In vivo assays demonstrated that PF reduced the expression levels of Hpa-1, increased the expression levels of ZO-1 and attenuated glycocalyx degradation in the glomerulus. These data suggested that PF attenuated HG-induced filtration barrier injury of GEnC by regulating AMPK expression.
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Affiliation(s)
- Yong-Yu Yang
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
- Hunan Provincial Engineering Research Central of Translational Medical and Innovative Drug, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
| | - Zhuo Chen
- Department of Geriatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
| | - Xi-Ding Yang
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
| | - Rong-Rong Deng
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China
| | - Ling-Xing Shi
- Department of Pharmacology, Changsha Medical University, Changsha, Hunan 410219, P.R. China
| | - Liang-Yuan Yao
- Hunan Qianjin Xiangjiang Pharmaceutical Industry Co., Ltd., Zhuzhou, Hunan 412000, P.R. China
| | - Da-Xiong Xiang
- Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
- Hunan Provincial Engineering Research Central of Translational Medical and Innovative Drug, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
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44
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Puchwein-Schwepcke A, Genzel-Boroviczény O, Nussbaum C. The Endothelial Glycocalyx: Physiology and Pathology in Neonates, Infants and Children. Front Cell Dev Biol 2021; 9:733557. [PMID: 34540845 PMCID: PMC8440834 DOI: 10.3389/fcell.2021.733557] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 08/12/2021] [Indexed: 11/13/2022] Open
Abstract
The endothelial glycocalyx (EG) as part of the endothelial surface layer (ESL) is an important regulator of vascular function and homeostasis, including permeability, vascular tone, leukocyte recruitment and coagulation. Located at the interface between the endothelium and the blood stream, this highly fragile structure is prone to many disruptive factors such as inflammation and oxidative stress. Shedding of the EG has been described in various acute and chronic diseases characterized by endothelial dysfunction and angiopathy, such as sepsis, trauma, diabetes and cardiovascular disease. Circulating EG components including syndecan-1, hyaluronan and heparan sulfate are being evaluated in animal and clinical studies as diagnostic and prognostic markers in several pathologies, and advances in microscopic techniques have enabled in vivo assessment of the EG. While research regarding the EG in adult physiology and pathology has greatly advanced throughout the last decades, our knowledge of the development of the glycocalyx and its involvement in pathological conditions in the pediatric population is limited. Current evidence suggests that the EG is present early during fetal development and plays a critical role in vessel formation and maturation. Like in adults, EG shedding has been demonstrated in acute inflammatory conditions in infants and children and chronic diseases with childhood-onset. However, the underlying mechanisms and their contribution to disease manifestation and progression still need to be established. In the future, the glycocalyx might serve as a marker to identify pediatric patients at risk for vascular sequelae and as a potential target for early interventions.
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Affiliation(s)
- Alexandra Puchwein-Schwepcke
- Division of Neonatology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.,Department of Pediatric Neurology and Developmental Medicine, University of Basel Children's Hospital, Basel, Switzerland
| | - Orsolya Genzel-Boroviczény
- Division of Neonatology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Claudia Nussbaum
- Division of Neonatology, Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany
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45
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Vlcek JR, Reynolds MM, Kipper MJ. Enzymatic Degradation of Glycosaminoglycans and Proteoglycan-Mimetic Materials in Solution and on Polyelectrolyte Multilayer Surfaces. Biomacromolecules 2021; 22:3913-3925. [PMID: 34347454 DOI: 10.1021/acs.biomac.1c00720] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Proteoglycans (PGs) play many important roles in biology, contributing to the mechanical properties of tissues, helping to organize extracellular matrix components, and participating in signaling mechanisms related to mechanotransduction, cell differentiation, immune responses, and wound healing. Our lab has designed two different types of PG mimics: polyelectrolyte complex nanoparticles (PCNs) and PG-mimetic graft copolymers (GCs), both of which are prepared using naturally occurring glycosaminoglycans. This work evaluates the enzymatic stability of these PG mimics using hyaluronidases (I-S, IV-S, and II), chondroitinase ABC, and lysozyme, for PG mimics suspended in solution and adsorbed onto surfaces. Hyaluronan (HA)- and chondroitin sulfate (CS)-containing PG mimics are degraded by the hyaluronidases. PCNs prepared with CS and GCs prepared with heparin are the only CS- and HA-containing PG mimics protected from chondroitinase ABC. None of the materials are measurably degraded by lysozyme. Adsorption to polyelectrolyte multilayer surfaces protects PG mimics from degradation, compared to when PG mimics are combined with enzymes in solution; all surfaces are still intact after 21 days of enzyme exposure. This work reveals how the stability of PG mimics is controlled by both the composition and macromolecular assembly of the PG mimic and also by the size and specificity of the enzyme. Understanding and tuning these degradation susceptibilities are essential for advancing their applications in cardiovascular materials, orthopedic materials, and growth factor delivery applications.
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Affiliation(s)
- Jessi R Vlcek
- School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523, United States
| | - Melissa M Reynolds
- School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523, United States.,School of Advanced Materials Discovery, Colorado State University, Fort Collins, Colorado 80523, United States.,School of Advanced Materials Discovery, Colorado State University, Fort Collins, Colorado 80523, United States
| | - Matt J Kipper
- School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523, United States.,School of Advanced Materials Discovery, Colorado State University, Fort Collins, Colorado 80523, United States.,Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado 80523, United States
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46
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Zhang Y, Zeng J, He X, Cao W, Peng X, Li G. Pulsatility protects the endothelial glycocalyx during extracorporeal membrane oxygenation. Microcirculation 2021; 28:e12722. [PMID: 34242445 DOI: 10.1111/micc.12722] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 05/03/2021] [Accepted: 07/05/2021] [Indexed: 01/06/2023]
Abstract
BACKGROUND Pulsatile flow protects vital organ function and improves microcirculatory perfusion during extracorporeal membrane oxygenation (ECMO). Studies revealed that pulsatile shear stress plays a vital role in microcirculatory function and integrity. The objective of this study was to investigate how pulsatility affects wall shear stress and endothelial glycocalyx components during ECMO. METHODS Using the i-Cor system, sixteen canine ECMO models were randomly allocated into the pulsatile or the non-pulsatile group (eight canines for each). Hemodynamic parameters, peak wall shear stress (PWSS), serum concentration of syndecan-1, and heparan sulfate were measured at different time points during ECMO. Pulsatile shear stress experiments were also performed in endothelial cells exposed to different magnitudes of pulsatility (five plates for each condition), with cell viability, the expressions of syndecan-1, and endothelial-to-mesenchymal transformation (EndMT) markers analyzed. RESULTS The pulsatile flow generated more surplus hemodynamic energy and preserved higher PWSS during ECMO. Serum concentrations of both syndecan-1 and heparan sulfate were negatively correlated with PWSS, and significantly lower levels were observed in the pulsatile group. Besides, non-pulsatility triggered EndMT and endothelial cells exposed to low pulsatility had the lowest possibility of EndMT. CONCLUSION The maintenance of the PWSS by pulsatility during ECMO possesses beneficial effects on glycocalyx integrity. Moreover, pulsatility prevents EndMT in endothelial cells, and low pulsatility exhibits the best protective effects. The augmentation of pulsatility may be a plausible future direction to improve the clinical outcome in ECMO.
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Affiliation(s)
- Yu Zhang
- Department of Pathology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jianfeng Zeng
- Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaoqian He
- Department of Obstetrics and Gynecology, Guangzhou Women and Children`s Medical Center, Guangzhou Medical University, Guangzhou, China
| | - Weidong Cao
- Department of Cardiothoracic Surgery, Dongguan People's Hospital, Affiliated Dongguan People's Hospital of Southern Medical University, Dongguan, China
| | - Xiaopeng Peng
- Department of Cardiothoracic Surgery, Dongguan People's Hospital, Affiliated Dongguan People's Hospital of Southern Medical University, Dongguan, China
| | - Guanhua Li
- Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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47
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Whitmore HAB, Kim LA. Understanding the Role of Blood Vessels in the Neurologic Manifestations of Coronavirus Disease 2019 (COVID-19). THE AMERICAN JOURNAL OF PATHOLOGY 2021; 191:1946-1954. [PMID: 34126084 PMCID: PMC8193973 DOI: 10.1016/j.ajpath.2021.04.017] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 04/18/2021] [Accepted: 04/26/2021] [Indexed: 12/21/2022]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originally identified as an outbreak in Wuhan, China, toward the end of 2019 and quickly became a global pandemic, with a large death toll. Originally identified as a respiratory disease, similar to previously discovered SARS and Middle East respiratory syndrome (MERS), concern has since been raised about the effects of SARS-CoV-2 infection on the vasculature. This viral-vascular involvement is of particular concern with regards to the small vessels present in the brain, with mounting evidence demonstrating that SARS-CoV-2 is capable of crossing the blood-brain barrier. Severe symptoms, termed coronavirus disease 2019 (COVID-19), often result in neurologic complications, regardless of patient age. These neurologic complications range from mild to severe across all demographics; however, the long-term repercussions of neurologic involvement on patient health are still unknown.
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Affiliation(s)
- Hannah A B Whitmore
- Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
| | - Leo A Kim
- Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
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48
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Guerrero JI, Barragán LA, Martínez JD, Montoya JP, Peña A, Sobrino FE, Tovar-Spinoza Z, Ghotme KA. Central and peripheral nervous system involvement by COVID-19: a systematic review of the pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings. BMC Infect Dis 2021; 21:515. [PMID: 34078305 PMCID: PMC8170436 DOI: 10.1186/s12879-021-06185-6] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 05/14/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND SARS-CoV-2 can affect the human brain and other neurological structures. An increasing number of publications report neurological manifestations in patients with COVID-19. However, no studies have comprehensively reviewed the clinical and paraclinical characteristics of the central and peripheral nervous system's involvement in these patients. This study aimed to describe the features of the central and peripheral nervous system involvement by COVID-19 in terms of pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings. METHODS We conducted a comprehensive systematic review of all the original studies reporting patients with neurological involvement by COVID-19, from December 2019 to June 2020, without language restriction. We excluded studies with animal subjects, studies not related to the nervous system, and opinion articles. Data analysis combined descriptive measures, frequency measures, central tendency measures, and dispersion measures for all studies reporting neurological conditions and abnormal ancillary tests in patients with confirmed COVID-19. RESULTS A total of 143 observational and descriptive studies reported central and peripheral nervous system involvement by COVID-19 in 10,723 patients. Fifty-one studies described pathophysiologic mechanisms of neurological involvement by COVID-19, 119 focused on clinical manifestations, 4 described neuropathology findings, 62 described neuroimaging findings, 28 electrophysiology findings, and 60 studies reported cerebrospinal fluid results. The reviewed studies reflect a significant prevalence of the nervous system's involvement in patients with COVID-19, ranging from 22.5 to 36.4% among different studies, without mortality rates explicitly associated with neurological involvement by SARS-CoV-2. We thoroughly describe the clinical and paraclinical characteristics of neurological involvement in these patients. CONCLUSIONS Our evidence synthesis led to a categorical analysis of the central and peripheral neurological involvement by COVID-19 and provided a comprehensive explanation of the reported pathophysiological mechanisms by which SARS-CoV-2 infection may cause neurological impairment. International collaborative efforts and exhaustive neurological registries will enhance the translational knowledge of COVID-19's central and peripheral neurological involvement and generate therapeutic decision-making strategies. REGISTRATION This review was registered in PROSPERO 2020 CRD42020193140 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020193140.
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Affiliation(s)
- Juan I. Guerrero
- Translational Neuroscience Research Lab, Faculty of Medicine, Universidad de La Sabana, Autopista Norte, KM 7, Chía, 250001 Colombia
| | - Luis A. Barragán
- Translational Neuroscience Research Lab, Faculty of Medicine, Universidad de La Sabana, Autopista Norte, KM 7, Chía, 250001 Colombia
| | - Juan D. Martínez
- Translational Neuroscience Research Lab, Faculty of Medicine, Universidad de La Sabana, Autopista Norte, KM 7, Chía, 250001 Colombia
| | - Juan P. Montoya
- Translational Neuroscience Research Lab, Faculty of Medicine, Universidad de La Sabana, Autopista Norte, KM 7, Chía, 250001 Colombia
| | - Alejandra Peña
- Translational Neuroscience Research Lab, Faculty of Medicine, Universidad de La Sabana, Autopista Norte, KM 7, Chía, 250001 Colombia
| | - Fidel E. Sobrino
- Translational Neuroscience Research Lab, Clinical Neurology Program, Universidad de La Sabana, Autopista Norte, KM 7, Chía, 250001 Colombia
- Neurology Unit, Hospital Occidente de Kennedy, Bogota, Colombia
| | - Zulma Tovar-Spinoza
- Pediatric Neurosurgery, Pediatric Epilepsy Surgery, Neurosurgical Laser Ablation Program, Upstate University Hospital, 750 East Adams Street, Syracuse, NY 13210 USA
| | - Kemel A. Ghotme
- Translational Neuroscience Research Lab, Faculty of Medicine, Universidad de La Sabana, Autopista Norte, KM 7, Chía, 250001 Colombia
- Pediatric Neurosurgery, Department of Neurosurgery, Fundacion Santa Fe de Bogota, Bogota, Colombia
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49
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Walter FR, Santa-Maria AR, Mészáros M, Veszelka S, Dér A, Deli MA. Surface charge, glycocalyx, and blood-brain barrier function. Tissue Barriers 2021; 9:1904773. [PMID: 34003072 DOI: 10.1080/21688370.2021.1904773] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
The negative surface charge of brain microvessel endothelial cells is derived from the special composition of their membrane lipids and the thick endothelial surface glycocalyx. They are important elements of the unique defense systems of the blood-brain barrier. The tissue-specific properties, components, function and charge of the brain endothelial glycocalyx have only been studied in detail in the past 15 years. This review highlights the importance of the negative surface charge in the permeability of macromolecules and nanoparticles as well as in drug interactions. We discuss surface charge and glycoxalyx changes in pathologies related to the brain microvasculature and protective measures against glycocalyx shedding and damage. We present biophysical techniques, including a microfluidic chip device, to measure surface charge of living brain endothelial cells and imaging methods for visualization of surface charge and glycocalyx.
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Affiliation(s)
- Fruzsina R Walter
- Institute of Biophysics, Biological Research Centre, Szeged, Hungary.,Department of Biotechnology, University of Szeged, Szeged, Hungary
| | - Ana R Santa-Maria
- Institute of Biophysics, Biological Research Centre, Szeged, Hungary.,Doctoral School of Biology, University of Szeged, Szeged, Hungary
| | - Mária Mészáros
- Institute of Biophysics, Biological Research Centre, Szeged, Hungary
| | - Szilvia Veszelka
- Institute of Biophysics, Biological Research Centre, Szeged, Hungary
| | - András Dér
- Institute of Biophysics, Biological Research Centre, Szeged, Hungary
| | - Mária A Deli
- Institute of Biophysics, Biological Research Centre, Szeged, Hungary
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50
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SARS-CoV-2-Associated Obliterative Arteritis Causing Massive Testicular Infarction. Clin Pract 2021; 11:246-249. [PMID: 34066311 PMCID: PMC8161438 DOI: 10.3390/clinpract11020037] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/12/2021] [Accepted: 04/21/2021] [Indexed: 12/24/2022] Open
Abstract
A 26-year-old man with symptomatic SARS-CoV-2 infection developed a sudden-onset acute testicular pain. The echo-doppler images showed massive testicular infarction, so orchiectomy was performed. On gross examination, the surgical specimen showed complete testicular necrosis and diffuse thickening of the testicular coverings. Under the microscope, a severe obliterative arteritis was evidenced. SARS-CoV-2 spike antibody was detected by immunohistochemistry in the arterial endothelium. Electron microscopy displayed intracytoplasmic spiky viral particles in endothelial cells. The patient was treated with corticoids and was asymptomatic at last contact.
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