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George Pryzdial EL, Perrier JR, Rashid MU, West HE, Sutherland MR. Viral coagulation: pushing the envelope. J Thromb Haemost 2024; 22:3366-3382. [PMID: 39260743 DOI: 10.1016/j.jtha.2024.08.014] [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: 02/27/2024] [Revised: 07/11/2024] [Accepted: 08/19/2024] [Indexed: 09/13/2024]
Abstract
Many virus types affect the blood clotting system with correlations to pathology that range widely from thrombosis to hemorrhage linking to inflammation. Here we overview the intricate crosstalk induced by infection between proteins on the virus encoded by either the host or virus genomes, coagulation proteins, platelets, leukocytes, and endothelial cells. For blood-borne viruses with an outer covering acquired from the host cell, the envelope, a key player may be the cell-derived trigger of coagulation on the virus surface, tissue factor (TF). TF is a multifunctional transmembrane cofactor that accelerates factor (F)VIIa-dependent activation of FX to FXa, leading to clot formation. However, the nascent TF/FVIIa/FXa complex also facilitates G protein-coupled modulation of cells via protease-activated receptor 2. As a viral envelope constituent, TF can bypass the physiological modes of regulation, thereby initiating the activation of neighboring platelets, leukocytes, and endothelial cells. A thromboinflammatory environment is predicted due to feedback amplification in response to cellular release of cytokines, procoagulant proteins, neutrophil extracellular traps, and stimulus-induced accessibility of adhesive receptors, resulting in cellular aggregates. The pathobiological effects of thromboinflammation ultimately contribute to innate and adaptive immunity for viral clearance. In contrast, the preceding stages of viral infection may be enhanced via the TF-protease axis.
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Affiliation(s)
- Edward Louis George Pryzdial
- Centre for Blood Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Division of Medical Affairs and Innovation, Canadian Blood Services, Ottawa, Ontario, Canada.
| | - John Ruggles Perrier
- Centre for Blood Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Division of Medical Affairs and Innovation, Canadian Blood Services, Ottawa, Ontario, Canada
| | - Mahamud-Ur Rashid
- Centre for Blood Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Division of Medical Affairs and Innovation, Canadian Blood Services, Ottawa, Ontario, Canada
| | - Henry Euan West
- Centre for Blood Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Division of Medical Affairs and Innovation, Canadian Blood Services, Ottawa, Ontario, Canada
| | - Michael Ross Sutherland
- Centre for Blood Research, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Division of Medical Affairs and Innovation, Canadian Blood Services, Ottawa, Ontario, Canada
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Shen T, Li Y, Liu T, Lian Y, Kong L. Association between Mycoplasma pneumoniae infection, high‑density lipoprotein metabolism and cardiovascular health (Review). Biomed Rep 2024; 20:39. [PMID: 38357242 PMCID: PMC10865299 DOI: 10.3892/br.2024.1729] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 01/09/2024] [Indexed: 02/16/2024] Open
Abstract
The association between Mycoplasma pneumoniae (M. pneumoniae) infection, high-density lipoprotein metabolism and cardiovascular disease is an emerging research area. The present review summarizes the basic characteristics of M. pneumoniae infection and its association with high-density lipoprotein and cardiovascular health. M. pneumoniae primarily invades the respiratory tract and damages the cardiovascular system through various mechanisms including adhesion, invasion, secretion of metabolites, production of autoantibodies and stimulation of cytokine production. Additionally, the present review highlights the potential role of high-density lipoprotein for the development of prevention and intervention of M. pneumoniae infection and cardiovascular disease, and provides suggestions for future research directions and clinical practice. It is urgent to explore the specific mechanisms underlying the association between M. pneumoniae infection, high-density lipoprotein metabolism, and cardiovascular disease and analyze the roles of the immune system and inflammatory response.
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Affiliation(s)
- Tao Shen
- Department of Clinical Laboratory, Jincheng People's Hospital, Jincheng, Shanxi 048000, P.R. China
- Jincheng Hospital Affiliated to Changzhi Medical College, Jincheng, Shanxi 048000, P.R. China
| | - Yanfang Li
- Department of Clinical Laboratory, Jincheng People's Hospital, Jincheng, Shanxi 048000, P.R. China
- Jincheng Hospital Affiliated to Changzhi Medical College, Jincheng, Shanxi 048000, P.R. China
| | - Tingting Liu
- Department of Clinical Laboratory, Jincheng People's Hospital, Jincheng, Shanxi 048000, P.R. China
- Jincheng Hospital Affiliated to Changzhi Medical College, Jincheng, Shanxi 048000, P.R. China
| | - Yunzhi Lian
- Department of Clinical Laboratory, Jincheng People's Hospital, Jincheng, Shanxi 048000, P.R. China
- Jincheng Hospital Affiliated to Changzhi Medical College, Jincheng, Shanxi 048000, P.R. China
| | - Luke Kong
- Department of Clinical Laboratory, Jincheng People's Hospital, Jincheng, Shanxi 048000, P.R. China
- Jincheng Hospital Affiliated to Changzhi Medical College, Jincheng, Shanxi 048000, P.R. China
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Abstract
Sepsis is accompanied by thrombocytopenia and the severity of the thrombocytopenia is associated with mortality. This thrombocytopenia is characteristic of disseminated intravascular coagulation (DIC), the sepsis-associated coagulopathy. Many of the pathogens, both bacterial and viral, that cause sepsis also directly activate platelets, which suggests that pathogen-induced platelet activation leads to systemic thrombosis and drives the multi-organ failure of DIC. In this paper we review the mechanisms of platelet activation by pathogens and the evidence for a role for anti-platelet agents in the management of sepsis.
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Affiliation(s)
- Dermot Cox
- School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
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4
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Pejcic A, Kostic M, Marko I, Obradovic R, Minic I, Bradic-Vasic M, Gligorijevic N, Kurtagic D. Tooth loss and periodontal status in patients with cardiovascular disease in the Serbian population: A randomized prospective study. Int J Dent Hyg 2022; 21:317-327. [PMID: 36578147 DOI: 10.1111/idh.12663] [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: 09/05/2021] [Revised: 12/26/2022] [Accepted: 12/28/2022] [Indexed: 12/30/2022]
Abstract
OBJECTIVES Chronic periodontal infections may predispose to cardiovascular disease. Since tooth loss may be due to periodontitis it is assumed that tooth loss can also predisposes cardiovascular disease. The aim was to investigate the possible relationship between the severity of the clinical picture of periodontitis and the occurrence of cardiovascular disease. METHODS We evaluated the association between clinical periodontal parameters, tooth loss and cardiovascular incident. A total of 100 subjects (50 subjects diagnosed with cardiovascular disease and 50 in control group without cardiovascular disease) underwent a dental examination. Tooth loss in all participants was caused only as a consequence of periodontitis. In addition to periodontal status, conventional risk factors for cardiovascular diseases (hypertension, smoking, obesity, hypercholesterolemia, diabetes) were measured, too. RESULTS Periodontal status was worse in patients in the group with cardiovascular disease compared to the group without cardiovascular disease. A significant association was observed between tooth loss levels and cardiovascular disease. In the group of patients who had cardiovascular disease, tooth loss was more than 50%. In the group of patients without cardiovascular disease, tooth loss was about 20% of the total number of teeth. A significant association was observed between tooth loss levels and cardiovascular disease prevalence. CONCLUSION This study presents relationship between number of teeth and cardiovascular disease, indicating a link between oral health and cardiovascular disease.
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Affiliation(s)
- Ana Pejcic
- Department of Periodontology and Oral Medicine, Clinic of Dental Medicine, Medical Faculty, University of Nis, Nis, Serbia
| | - Milena Kostic
- Department of Prosthodontics, Clinic of Dental Medicine, Medical Faculty, University of Nis, Nis, Serbia
| | - Igic Marko
- Department of Prosthodontics, Clinic of Dental Medicine, Medical Faculty, University of Nis, Nis, Serbia
| | - Radmila Obradovic
- Department of Periodontology and Oral Medicine, Clinic of Dental Medicine, Medical Faculty, University of Nis, Nis, Serbia
| | - Ivan Minic
- Postdoctoral Study, Department of Periodontology and Oral Medicine, Medical Faculty, University of Nis, Nis, Serbia
| | - Marija Bradic-Vasic
- Postdoctoral Study, Department of Periodontology and Oral Medicine, Medical Faculty, University of Nis, Nis, Serbia
| | - Nikola Gligorijevic
- Postdoctoral Study, Department of Prosthodontics, Medical Faculty, University of Nis, Nis, Serbia
| | - Dzemil Kurtagic
- Postdoctoral Study, Department of Periodontology and Oral Medicine, Medical Faculty, University of Nis, Nis, Serbia
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Ghamar Talepoor A, Doroudchi M. Immunosenescence in atherosclerosis: A role for chronic viral infections. Front Immunol 2022; 13:945016. [PMID: 36059478 PMCID: PMC9428721 DOI: 10.3389/fimmu.2022.945016] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/26/2022] [Indexed: 01/10/2023] Open
Abstract
Immune system is a versatile and dynamic body organ which offers survival and endurance of human beings in their hostile living environment. However, similar to other cells, immune cells are hijacked by senescence. The ageing immune cells lose their beneficial functions but continue to produce inflammatory mediators which draw other immune and non-immune cells to the senescence loop. Immunosenescence has been shown to be associated with different pathological conditions and diseases, among which atherosclerosis has recently come to light. There are common drivers of both immunosenescence and atherosclerosis; e.g. inflammation, reactive oxygen species (ROS), chronic viral infections, genomic damage, oxidized-LDL, hypertension, cigarette smoke, hyperglycaemia, and mitochondrial failure. Chronic viral infections induce inflammaging, sustained cytokine signaling, ROS generation and DNA damage which are associated with atherogenesis. Accumulating evidence shows that several DNA and RNA viruses are stimulators of immunosenescence and atherosclerosis in an interrelated network. DNA viruses such as CMV, EBV and HBV upregulate p16, p21 and p53 senescence-associated molecules; induce inflammaging, metabolic reprogramming of infected cells, replicative senescence and telomere shortening. RNA viruses such as HCV and HIV induce ROS generation, DNA damage, induction of senescence-associated secretory phenotype (SASP), metabolic reprogramming of infected cells, G1 cell cycle arrest, telomere shortening, as well as epigenetic modifications of DNA and histones. The newly emerged SARS-CoV-2 virus is also a potent inducer of cytokine storm and SASP. The spike protein of SARS-CoV-2 promotes senescence phenotype in endothelial cells by augmenting p16, p21, senescence-associated β-galactosidase (SA-β-Gal) and adhesion molecules expression. The impact of SARS-CoV-2 mega-inflammation on atherogenesis, however, remains to be investigated. In this review we focus on the common processes in immunosenescence and atherogenesis caused by chronic viral infections and discuss the current knowledge on this topic.
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Pupina N, Avarlaid A, Sadam H, Pihlak A, Jaago M, Tuvikene J, Rähni A, Planken A, Planken M, Kalso E, Tienari PJ, Nieminen JK, Seppänen MRJ, Vaheri A, Lindholm D, Sinisalo J, Pussinen P, Timmusk T, Palm K. Immune response to a conserved enteroviral epitope of the major capsid VP1 protein is associated with lower risk of cardiovascular disease. EBioMedicine 2022; 76:103835. [PMID: 35091341 PMCID: PMC8801986 DOI: 10.1016/j.ebiom.2022.103835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 01/09/2022] [Accepted: 01/11/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Major cardiac events including myocardial infarction (MI) are associated with viral infections. However, how specific infections contribute to the cardiovascular insults has remained largely unclear. METHODS We employed next generation phage display mimotope-variation analysis (MVA) to explore the link between antibody-based immune response and severe cardiovascular conditions. Here, we used a case-control design, including the first-stage discovery cohort (n = 100), along with cohorts for second-stage discovery (n = 329) and validation (n = 466). FINDINGS We observed strong antibody response to the peptide antigens with Gly-Ile-X-Asp (G-I-X-D) core structure in healthy individuals but not in patients with MI. Analysis of the origin of this epitope linked it with the N-terminus of the VP1 protein of poliovirus 3 (PV3), but also other species of picornaviruses. Consistently, we found low levels of antibody response to the G-I-X-D epitope in individuals with severe cardiac disease complications. INTERPRETATION Our findings imply that antibody response to the G-I-X-D epitope is associated with polio vaccinations and that high antibody levels to this epitope could discriminate healthy individuals from prospective MI patients as a blood-derived biomarker. Together, these findings highlight the importance of epitope-specific antibody response and suggest that protective immunity against the polio- and non-polio enteroviral infections support improved cardiovascular health. FUNDING Estonian Ministry of Education (5.1-4/20/170), Estonian Research Council (PRG573, PRG805), H2020-MSCA-RISE-2016 (EU734791), H2020 PANBioRA (EU760921), European Union through the European Regional Development Fund (Project no. 2014-2020.4.01.15-0012), Helsinki University Hospital grants, Mary and Georg C. Ehrnrooth Foundation, Finnish Eye Foundation, Finska Läkaresällskapet, The Finnish Society of Sciences and Letters, Magnus Ehrnrooth Foundation and Sigrid Jusélius Foundation.
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Affiliation(s)
| | - Annela Avarlaid
- Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia
| | - Helle Sadam
- Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia
| | - Arno Pihlak
- Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia
| | - Mariliis Jaago
- Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia
| | - Jürgen Tuvikene
- Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia; dxlabs LLC, Mäealuse 4, Tallinn 12618, Estonia
| | - Annika Rähni
- Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia
| | - Anu Planken
- The North Estonia Medical Center, Tallinn, Estonia
| | | | - Eija Kalso
- Department of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University Hospital and Department of Pharmacology and SleepWell Research Programme, University of Helsinki, Finland
| | - Pentti J Tienari
- Department of Neurology, Neurocenter, Helsinki University Hospital, and Translational Immunology Research Program, University of Helsinki, Finland
| | - Janne K Nieminen
- Department of Neurology, Neurocenter, Helsinki University Hospital, and Translational Immunology Research Program, University of Helsinki, Finland
| | - Mikko R J Seppänen
- Department of Neurology, Neurocenter, Helsinki University Hospital, and Translational Immunology Research Program, University of Helsinki, Finland
| | - Antti Vaheri
- Department of Virology, Medicum, University of Helsinki, Finland
| | - Dan Lindholm
- Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland
| | - Juha Sinisalo
- Heart and Lung Center, Helsinki University Hospital, University of Helsinki, Finland
| | - Pirkko Pussinen
- Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Finland
| | - Tõnis Timmusk
- Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia
| | - Kaia Palm
- Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia; Department of Chemistry and Biotechnology, Tallinn University of Technology, Estonia.
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Masoud MM, Sayed HA, El Masry HA, Abdelkareem SA. HCV co-infection is related to acute ischemic severity and outcome. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.1186/s43162-021-00095-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background and aim
HCV infection is associated with increased risk of ischemic cerebral stroke. HCV stroked patients are younger with a lower burden of classical risk factors and higher levels of systemic inflammation. The present study aimed to discover the association between HCV infection functional outcome of stroke.
Patients and methods
The present prospective study included 60 patients with acute ischemic stroke. All patients were subjected to careful history taking and through clinical and neurological examination. Stroke severity at presentation was assessed using National Institute of Health Stroke Scale (NIHSS). Quantitative HCV RNA test was used to diagnose HCV infection. The prognosis of the studied patients was 3 months after treatment using modified Rankin scale (mRS) for neurologic disability.
Results
The present study was conducted on 60 patients with ischemic stroke. They comprised 13 patients (21.7%) with HCV and 47 patients without. Stroke patients with HCV had significantly higher frequency of carotid artery stenosis, higher NIHSS (17.9 ± 6.9 versus 9.9 ± 5.3, p < 0.001) and higher frequency of severe stroke (46.1% versus 4.3%, p = 0.001) when compared with patients without HCV. Logistic regression analysis identified patients’ sex, NIHSS and HCV as significant predictors of outcome in univariate analysis. However, in multivariate analysis, only NIHSS proved to be significant.
Conclusions
The present study suggests a significant link between chronic HCV infection and ischemic stroke severity and poor outcome. This is probably related to the pathogenic effects of the chronic inflammatory state induced by HCV infection on the cerebral microvasculature.
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8
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De Pasquale C, Campana S, Bonaccorsi I, Carrega P, Ferlazzo G. ILC in chronic inflammation, cancer and targeting with biologicals. Mol Aspects Med 2021; 80:100963. [PMID: 33726947 DOI: 10.1016/j.mam.2021.100963] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 11/11/2020] [Accepted: 03/04/2021] [Indexed: 12/14/2022]
Abstract
Since their discovery, Innate Lymphoid Cells (ILC) have emerged as important effector cells, serving multiple roles in maintaining tissue homeostasis and responding to tissue insults. As such, dysregulations of their function and distribution have been observed in a variety of immune-mediated diseases, suggesting a specific role for ILC in the pathophysiology of several disorders including chronic inflammation and cancer. Here, we provide an updated view on ILC biology dissecting their pathological or protective contribution in chronic inflammatory diseases such as multiple sclerosis, inflammatory bowel diseases, psoriasis, rheumatoid arthritis, asthma and COPD, atherosclerosis, also exploring ILC role in tumor surveillance and progression. Throughout the review, we will also highlight how the potential dual role of these cells for protective or pathogenic immunity in many inflammatory diseases makes them interesting targets for the development of novel therapeutic strategies, particularly promising.
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Affiliation(s)
- Claudia De Pasquale
- Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, Italy
| | - Stefania Campana
- Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, Italy
| | - Irene Bonaccorsi
- Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, Italy; Cell Factory Center and Division of Clinical Pathology, University Hospital Policlinico G.Martino, Messina, Italy
| | - Paolo Carrega
- Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, Italy
| | - Guido Ferlazzo
- Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, Italy; Cell Factory Center and Division of Clinical Pathology, University Hospital Policlinico G.Martino, Messina, Italy.
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9
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Elkind MSV, Boehme AK, Smith CJ, Meisel A, Buckwalter MS. Infection as a Stroke Risk Factor and Determinant of Outcome After Stroke. Stroke 2020; 51:3156-3168. [PMID: 32897811 DOI: 10.1161/strokeaha.120.030429] [Citation(s) in RCA: 164] [Impact Index Per Article: 32.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Understanding the relationship between infection and stroke has taken on new urgency in the era of the coronavirus disease 2019 (COVID-19) pandemic. This association is not a new concept, as several infections have long been recognized to contribute to stroke risk. The association of infection and stroke is also bidirectional. Although infection can lead to stroke, stroke also induces immune suppression which increases risk of infection. Apart from their short-term effects, emerging evidence suggests that poststroke immune changes may also adversely affect long-term cognitive outcomes in patients with stroke, increasing the risk of poststroke neurodegeneration and dementia. Infections at the time of stroke may also increase immune dysregulation after the stroke, further exacerbating the risk of cognitive decline. This review will cover the role of acute infections, including respiratory infections such as COVID-19, as a trigger for stroke; the role of infectious burden, or the cumulative number of infections throughout life, as a contributor to long-term risk of atherosclerotic disease and stroke; immune dysregulation after stroke and its effect on the risk of stroke-associated infection; and the impact of infection at the time of a stroke on the immune reaction to brain injury and subsequent long-term cognitive and functional outcomes. Finally, we will present a model to conceptualize the many relationships among chronic and acute infections and their short- and long-term neurological consequences. This model will suggest several directions for future research.
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Affiliation(s)
- Mitchell S V Elkind
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY. (M.S.V.E., A.K.B.).,Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY. (M.S.V.E., A.K.B.)
| | - Amelia K Boehme
- Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY. (M.S.V.E., A.K.B.).,Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY. (M.S.V.E., A.K.B.)
| | - Craig J Smith
- Division of Cardiovascular Sciences, Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester Centre for Clinical Neurosciences, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Manchester, United Kingdom (C.J.S.)
| | - Andreas Meisel
- Center for Stroke Research Berlin, Department for Experimental Neurology, Department of Neurology, NeuroCure Clinical Research Center, Charité Universitätsmedizin Berlin, Germany (A.M.)
| | - Marion S Buckwalter
- Department of Neurology and Neurological Sciences, Stanford University Medical Center, CA (M.S.B.)
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Gerdes C, Werner C, Kloos C, Lehmann T, Wolf G, Müller UA, Müller N. Progression of Diabetic Complications in Subgroups of People with Long Term Diabetes Type 1 According to Clinical Course. Exp Clin Endocrinol Diabetes 2020; 130:101-109. [PMID: 32777840 DOI: 10.1055/a-1192-3761] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
AIMS Prevention and prediction of microvascular complications are important aims of medical care in people with type 1 diabetes. Since the course of the disease is heterogenous, we tried to identify subgroups with specific risk profiles for microvascular complications. METHODS Retrospective analysis of a cohort of 285 people (22637 consultations) with >10 years of type 1 diabetes. Persons were grouped into slow (<15 years), fast (>15 years) and non progressors according to the average onset of microvascular complications. Generalized estimating equations for binary outcomes were applied and pseudo coefficients of determination were calculated. RESULTS Progression to microvascular disease was associated with age (OR: 1.034 [1.001-1.068]; p=0.04), diabetes duration (OR: 1.057 [1.021-1.094]; p=0.002), HbA1c (OR: 1.035 [1.011-1.060]; p=0.005), BMI (OR: 0.928 [0.866-0.994]; p=0.034) and the social strata index (OR: 0.910 [0.830-0.998]; p=0.046). Generalized estimating equations predicted 31.02% and exclusion of HbA1c marginally reduced the value to 28.88%. The proportion of patients with LADA was higher in fast than slow progressors [13 (26.5%) vs. 14 (11.9%); p=0.019]. A generalized estimating equation comparing slow to fast progressors revealed no significant markers. CONCLUSION In our analysis, we were able to confirm known risk factors for microvascular disease in people with type 1 diabetes. Overall, prediction of individual risk was difficult, the effect of individual markers minor and we could not find differences regarding slow or fast progression. We therefore emphasis the need for additional markers to predict individual risk for microvascular disease.
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Affiliation(s)
- Christian Gerdes
- Department of Internal Medicine III, Jena University Hospital, Jena, Germany
| | - Christoph Werner
- Department of Internal Medicine III, Jena University Hospital, Jena, Germany
| | - Christof Kloos
- Department of Internal Medicine III, Jena University Hospital, Jena, Germany
| | - Thomas Lehmann
- Department of Medical Statistics, Jena University Hospital, Information and Documentation, Jena, Germany
| | - Gunter Wolf
- Department of Internal Medicine III, Jena University Hospital, Jena, Germany
| | - Ulrich Alfons Müller
- Department of Internal Medicine III, Jena University Hospital, Jena, Germany.,Practice for Endocrinology and Diabetes, Centre for Ambulatory Medicine, Jena University Hospital, Jena, Germany
| | - Nicolle Müller
- Department of Internal Medicine III, Jena University Hospital, Jena, Germany
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11
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Pryzdial ELG, Sutherland MR, Lin BH, Horwitz M. Antiviral anticoagulation. Res Pract Thromb Haemost 2020; 4:774-788. [PMID: 32685886 PMCID: PMC7354393 DOI: 10.1002/rth2.12406] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 05/28/2020] [Accepted: 06/08/2020] [Indexed: 02/06/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel envelope virus that causes coronavirus disease 2019 (COVID-19). Hallmarks of COVID-19 are a puzzling form of thrombophilia that has elevated D-dimer but only modest effects on other parameters of coagulopathy. This is combined with severe inflammation, often leading to acute respiratory distress and possible lethality. Coagulopathy and inflammation are interconnected by the transmembrane receptor, tissue factor (TF), which initiates blood clotting as a cofactor for factor VIIa (FVIIa)-mediated factor Xa (FXa) generation. TF also functions from within the nascent TF/FVIIa/FXa complex to trigger profound changes via protease-activated receptors (PARs) in many cell types, including SARS-CoV-2-trophic cells. Therefore, aberrant expression of TF may be the underlying basis of COVID-19 symptoms. Evidence suggests a correlation between infection with many virus types and development of clotting-related symptoms, ranging from heart disease to bleeding, depending on the virus. Since numerous cell types express TF and can act as sites for virus replication, a model envelope virus, herpes simplex virus type 1 (HSV1), has been used to investigate the uptake of TF into the envelope. Indeed, HSV1 and other viruses harbor surface TF antigen, which retains clotting and PAR signaling function. Strikingly, envelope TF is essential for HSV1 infection in mice, and the FXa-directed oral anticoagulant apixaban had remarkable antiviral efficacy. SARS-CoV-2 replicates in TF-bearing epithelial and endothelial cells and may stimulate and integrate host cell TF, like HSV1 and other known coagulopathic viruses. Combined with this possibility, the features of COVID-19 suggest that it is a TFopathy, and the TF/FVIIa/FXa complex is a feasible therapeutic target.
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Affiliation(s)
- Edward L. G. Pryzdial
- Center for InnovationCanadian Blood ServicesVancouverBCCanada
- Centre for Blood Research and Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverBCCanada
| | - Michael R. Sutherland
- Center for InnovationCanadian Blood ServicesVancouverBCCanada
- Centre for Blood Research and Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverBCCanada
| | - Bryan H. Lin
- Center for InnovationCanadian Blood ServicesVancouverBCCanada
- Centre for Blood Research and Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverBCCanada
| | - Marc Horwitz
- Department of Microbiology and ImmunologyUniversity of British ColumbiaVancouverBCCanada
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12
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Sutherland MR, Simon AY, Shanina I, Horwitz MS, Ruf W, Pryzdial ELG. Virus envelope tissue factor promotes infection in mice. J Thromb Haemost 2019; 17:482-491. [PMID: 30659719 PMCID: PMC6397068 DOI: 10.1111/jth.14389] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Indexed: 01/04/2023]
Abstract
Essentials The coagulation initiator, tissue factor (TF), is on the herpes simplex virus 1 (HSV1) surface. HSV1 surface TF was examined in mice as an antiviral target since it enhances infection in vitro. HSV1 surface TF facilitated infection of all organs evaluated and anticoagulants were antiviral. Protease activated receptor 2 inhibited infection in vivo and its pre-activation was antiviral. SUMMARY: Background Tissue factor (TF) is the essential cell surface initiator of coagulation, and mediates cell signaling through protease-activated receptor (PAR) 2. Having a diverse cellular distribution, TF is involved in many biological pathways and pathologies. Our earlier work identified host cell-derived TF on the envelope covering several viruses, and showed its involvement in enhanced cell infection in vitro. Objective In the current study, we evaluated the in vivo effects of virus surface TF on infection and on the related modulator of infection PAR2. Methods With the use of herpes simplex virus type 1 (HSV1) as a model enveloped virus, purified HSV1 was generated with or without envelope TF through propagation in a TF-inducible cell line. Infection was studied after intravenous inoculation of BALB/c, C57BL/6J or C57BL/6J PAR2 knockout mice with 5 × 105 plaque-forming units of HSV1, mimicking viremia. Three days after inoculation, organs were processed, and virus was quantified with plaque-forming assays and quantitative real-time PCR. Results Infection of brain, lung, heart, spinal cord and liver by HSV1 required viral TF. Demonstrating promise as a therapeutic target, virus-specific anti-TF mAbs or small-molecule inhibitors of coagulation inhibited infection. PAR2 modulates HSV1 in vivo as demonstrated with PAR2 knockout mice and PAR2 agonist peptide. Conclusion TF is a constituent of many permissive host cell types. Therefore, the results presented here may explain why many viruses are correlated with hemostatic abnormalities, and indicate that TF is a novel pan-specific envelope antiviral target.
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MESH Headings
- Animals
- Anticoagulants/pharmacology
- Antiviral Agents/pharmacology
- Disease Models, Animal
- Female
- Herpes Simplex/blood
- Herpes Simplex/drug therapy
- Herpes Simplex/immunology
- Herpes Simplex/virology
- Herpesvirus 1, Human/drug effects
- Herpesvirus 1, Human/immunology
- Herpesvirus 1, Human/metabolism
- Host-Pathogen Interactions
- Injections, Intravenous
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Receptor, PAR-2/genetics
- Receptor, PAR-2/metabolism
- Th1 Cells/immunology
- Th1 Cells/virology
- Thromboplastin/administration & dosage
- Thromboplastin/metabolism
- Viral Envelope Proteins/administration & dosage
- Viral Envelope Proteins/metabolism
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Affiliation(s)
- Michael R Sutherland
- Canadian Blood Services, Center for Innovation, Vancouver, Canada
- Centre for Blood Research and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
| | - Ayo Y Simon
- Canadian Blood Services, Center for Innovation, Vancouver, Canada
- Centre for Blood Research and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
- African Centre of Excellence on Neglected Tropical Diseases and Forensic Biotechnology and Veterinary Teaching Hospital, Ahmadu Bello University, Zaria, Nigeria
- Preclinical Research and Development, Emergent BioSolutions, Winnipeg, Manitoba, Canada
| | - Iryna Shanina
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
| | - Marc S Horwitz
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
| | - Wolfram Ruf
- Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA, USA
- Center for Thrombosis and Hemostasis, University Medical Center, Mainz, Germany
| | - Edward L G Pryzdial
- Canadian Blood Services, Center for Innovation, Vancouver, Canada
- Centre for Blood Research and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
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13
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Lidón F, Padilla S, García JA, Fernández M, García J, Ortiz de la Tabla V, Gutiérrez F, Masiá M. Contribution of Human Herpesvirus 8 and Herpes Simplex Type 2 to Progression of Carotid Intima-Media Thickness in People Living With HIV. Open Forum Infect Dis 2019; 6:ofz041. [PMID: 30815506 PMCID: PMC6386804 DOI: 10.1093/ofid/ofz041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 01/11/2019] [Accepted: 01/23/2019] [Indexed: 11/14/2022] Open
Abstract
Background Human herpesvirus 8 (HHV-8) is a lymphotropic and vasculotropic herpesvirus with potential pro-atherogenic effects. We explored the influence of coinfection with HHV-8 and other herpesviruses on the rate of progression of carotid intima-media thickness (cIMT) in virologically suppressed people living with HIV (PLWH). Methods Prospective cohort study including men who have sex with men (MSM) infected with HIV. At the baseline visit, IgG antibodies against HHV-8 and other herpesviruses, highly sensitive C-reactive protein (hsCRP) levels, and Framingham risk scores were measured. To evaluate the progression of cIMT, successive measurements with high-resolution carotid artery ultrasound were performed over an 8-year period. Adjusted general linear mixed models were used to assess factors associated with faster cIMT progression. Results One hundred forty-one participants with suppressed HIV-RNA (<200 copies/mL) at cIMT measurement during the study period were included. Forty-six (31.3%) were coinfected with HHV-8 and 76 (54%) with herpes simplex virus 2 (HSV-2). Factors associated with faster cIMT progression adjusting for CD4 cell counts, time between cIMT measurements, hepatitis C, varicella zoster virus, and cytomegalovirus coinfection were seropositivity for HHV-8 (P = .059), HSV-2+HHV-8 coinfection (P = .027), Framingham risk score (P = .057), and hsCRP (P = .027). Coinfection with HHV-8 was independently associated with higher levels of hsCRP (odds ratio, 1.09; 95% confidence interval, 1.02 to 1.17; P = .016). When hsCRP and HHV-8 were simultaneously included in the adjusted model, the relationship of HHV-8 with cIMT progression was attenuated. Conclusions HHV-8 might contribute to progression of cIMT with a more prominent role when it coinfects with HHV-2 in virologically suppressed PLWH, and this effect could be driven by systemic inflammation.
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Affiliation(s)
- Fernando Lidón
- Infectious Diseases Unit, Hospital General Universitario de Elche and Universidad Miguel Hernández, Alicante, Spain
| | - Sergio Padilla
- Infectious Diseases Unit, Hospital General Universitario de Elche and Universidad Miguel Hernández, Alicante, Spain
| | - Jose A García
- Statistics, Centro de Investigación Operativa, Universidad Miguel Hernández, Elche, Alicante, Spain
| | - Marta Fernández
- Infectious Diseases Unit, Hospital General Universitario de Elche and Universidad Miguel Hernández, Alicante, Spain
| | - Javier García
- Infectious Diseases Unit, Hospital General Universitario de Elche and Universidad Miguel Hernández, Alicante, Spain
| | | | - Félix Gutiérrez
- Infectious Diseases Unit, Hospital General Universitario de Elche and Universidad Miguel Hernández, Alicante, Spain
| | - Mar Masiá
- Infectious Diseases Unit, Hospital General Universitario de Elche and Universidad Miguel Hernández, Alicante, Spain
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14
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Osama A, Ashour Y, Abd El-Razek R, Monir D. Assessment of carotid intima-media thickness and carotid plaque formation among patients with ischemic stroke and hepatitis C virus infection. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2019. [DOI: 10.1186/s41983-019-0054-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
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15
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Hemmat N, Ebadi A, Badalzadeh R, Memar MY, Baghi HB. Viral infection and atherosclerosis. Eur J Clin Microbiol Infect Dis 2018; 37:2225-2233. [PMID: 30187247 DOI: 10.1007/s10096-018-3370-z] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 08/28/2018] [Indexed: 12/22/2022]
Abstract
Several risk factors have been described for the pathogenesis of atherosclerosis. Infectious diseases are suggested to be a causative factor, and some viruses have been studied for their relation with atherosclerotic diseases. Studies report two hypotheses, direct and indirect effects, for the role of viral infections in atherogenesis. Viruses are able to initiate atherosclerosis by two different pathways. They can exert their direct effects on atherogenesis by infecting vascular cells and then inducing inflammation in the endothelium and smooth muscle cells. Alternatively, they can also apply indirect effects by infecting non-vascular cells and inducing systemic inflammation. In this review, we consider the available data about the effects and correlations of DNA and RNA viruses on atherosclerosis.
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Affiliation(s)
- Nima Hemmat
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, PO Box 5165665931, Tabriz, Iran
| | - Amin Ebadi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, PO Box 5165665931, Tabriz, Iran
| | - Reza Badalzadeh
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Yousef Memar
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, PO Box 5165665931, Tabriz, Iran.,Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, PO Box 5165665931, Tabriz, Iran. .,Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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16
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Wallet SM, Puri V, Gibson FC. Linkage of Infection to Adverse Systemic Complications: Periodontal Disease, Toll-Like Receptors, and Other Pattern Recognition Systems. Vaccines (Basel) 2018; 6:E21. [PMID: 29621153 PMCID: PMC6027258 DOI: 10.3390/vaccines6020021] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 03/25/2018] [Accepted: 03/30/2018] [Indexed: 12/13/2022] Open
Abstract
Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs) that provide innate immune sensing of conserved pathogen-associated molecular patterns (PAMPs) to engage early immune recognition of bacteria, viruses, and protozoa. Furthermore, TLRs provide a conduit for initiation of non-infectious inflammation following the sensing of danger-associated molecular patterns (DAMPs) generated as a consequence of cellular injury. Due to their essential role as DAMP and PAMP sensors, TLR signaling also contributes importantly to several systemic diseases including cardiovascular disease, diabetes, and others. The overlapping participation of TLRs in the control of infection, and pathogenesis of systemic diseases, has served as a starting point for research delving into the poorly defined area of infection leading to increased risk of various systemic diseases. Although conflicting studies exist, cardiovascular disease, diabetes, cancer, rheumatoid arthritis, and obesity/metabolic dysfunction have been associated with differing degrees of strength to infectious diseases. Here we will discuss elements of these connections focusing on the contributions of TLR signaling as a consequence of bacterial exposure in the context of the oral infections leading to periodontal disease, and associations with metabolic diseases including atherosclerosis and type 2 diabetes.
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Affiliation(s)
- Shannon M Wallet
- Department of Oral Biology, College of Dental Medicine, University of Florida, Gainesville, FL 32610, USA.
| | - Vishwajeet Puri
- Department of Biomedical Sciences and Diabetes Institute, Ohio University, Athens, OH 45701, USA.
| | - Frank C Gibson
- Department of Oral Biology, College of Dental Medicine, University of Florida, Gainesville, FL 32610, USA.
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17
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Liou LS, Chang CY, Chen HJ, Tseng CH, Chen CY, Sung FC. Increased risk of peripheral arterial occlusive disease in patients with Bell's palsy using population data. PLoS One 2017; 12:e0188982. [PMID: 29216223 PMCID: PMC5720702 DOI: 10.1371/journal.pone.0188982] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 11/16/2017] [Indexed: 11/19/2022] Open
Abstract
Objective This population-based cohort study investigated the risk of developing peripheral arterial occlusive disease (PAOD) in patients with Bell’s palsy. Methods We used longitudinal claims data of health insurance of Taiwan to identify 5,152 patients with Bell’s palsy newly diagnosed in 2000–2010 and a control cohort of 20,608 patients without Bell’s palsy matched by propensity score. Incidence and hazard ratio (HR) of PAOD were assessed by the end of 2013. Results The incidence of PAOD was approximately 1.5 times greater in the Bell’s palsy group than in the non-Bell’s palsy controls (7.75 vs. 4.99 per 1000 person-years). The Cox proportional hazards regression analysis measured adjusted HR was 1.54 (95% confidence interval (CI) = 1.35–1.76) for the Bell’s palsy group compared to the non-Bell’s palsy group, after adjusting for sex, age, occupation, income and comorbidities. Men were at higher risk of PAOD than women in the Bell’s palsy group, but not in the controls. The incidence of PAOD increased with age in both groups, but the Bell’s palsy group to control group HR of PAOD decreased as age increased. The systemic steroid treatment reduced 13% of PAOD hazard for Bell’s palsy patients, compared to those without the treatment, but not significant. Conclusions Bell’s palsy appears to be associated with an increased risk of developing PAOD. Further pathophysiologic, histopathology and immunologic research is required to explore the underlying biologic mechanism.
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Affiliation(s)
- Li-Syue Liou
- Department of Family Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien City, Hualien County, Taiwan, ROC
- Department of Family Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Xindian Dist., New Taipei City, Taiwan(R.O.C)
- Department of Family and Community Medicine, Tri-Service General Hospital, Neihu District, Taipei City, Taiwan(R.O.C.)
- School of Medicine, National Defense Medical Center, Neihu Dist., Taipei City, aiwan (R.O.C.)
| | - Chih-Ya Chang
- School of Medicine, National Defense Medical Center, Neihu Dist., Taipei City, aiwan (R.O.C.)
- Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, Neihu District, Taipei City, Taiwan(R.O.C.)
| | - Hsuan-Ju Chen
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan, Taichung, Taichung, Taiwan (R.O.C.)
| | - Chun-Hung Tseng
- Department of Neurology, China Medical University Hospital, Taichung, Taiwan, North District, Taichung, Taiwan (R.O.C.)
- School of Medicine, China Medical University, Taichung, Taiwan, Taichung, Taichung, Taiwan (R.O.C.)
| | - Cheng-Yu Chen
- Department of Family Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Xindian Dist., New Taipei City, Taiwan(R.O.C)
| | - Fung-Chang Sung
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan, Taichung, Taichung, Taiwan (R.O.C.)
- Graduate Institute of Clinical Medicine Science, College of Medicine, China Medical University, Taichung, Taiwan; Taichung, Taichung, Taiwan (R.O.C.)
- Department of Health Services Administration, China Medical University, Taichung, Taiwan; Taichung, Taichung, Taiwan (R.O.C.)
- * E-mail:
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18
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Ford JL, Stowe RP. Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences. Psychoneuroendocrinology 2017; 86:128-133. [PMID: 28954244 PMCID: PMC5905709 DOI: 10.1016/j.psyneuen.2017.09.009] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 09/04/2017] [Accepted: 09/06/2017] [Indexed: 11/21/2022]
Abstract
BACKGROUND Adolescent females have a higher prevalence of depression in comparison to their male peers - a disparity that has been increasing over the past decade. Depression is of concern as it is associated with chronic disease and to immune dysregulation, which may be one mechanism linking depression to future pathology. This study examined the extent to which sex moderated the association between depressive symptoms and immune dysregulation during adolescence using Epstein-Barr virus (EBV) reactivation, a biomarker of cellular immune response, as a model. METHODS A representative community sample of 259 female and 279 male adolescents aged 11-17 years who were EBV IgG positive were examined. Trained interviewers collected the data during two home visits, one week apart. Depressive symptoms were measured at the first visit using the 9 item short-form of the Center for Epidemiologic Studies-Depression scale. EBV biomarkers were collected via saliva at the second visit and included a qualitative measure of EBV viral capsid antigen immunoglobulin G to assess prior EBV infection and a quantitative measure of EBV DNA to assess the number of viral copies shed in the saliva. RESULTS In multivariable logistic regression analyses, increasing depressive symptoms were significantly associated with salivary shedding of EBV DNA for adolescent females only (logit=0.66, se=0.30, p<0.05), and the interaction between sex and depressive symptoms on salivary shedding of EBV DNA was statistically significant (logit=-1.19, se=0.42, p<0.01). Sensitivity analyses were conducted in which sex was examined as a moderator in the relationship between depressive symptoms and salivary EBV DNA quantitative copies via Tobit regression; results were consistent with the presented findings. CONCLUSIONS Depressive symptoms are associated with EBV reactivation among EBV positive female adolescents, but not males. Future research is needed to examine EBV reactivation in female adolescents as a mechanism linking depression to future chronic disease and the role of sex hormones in explaining sex differences in the relationship between depressive symptoms and EBV reactivation.
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Affiliation(s)
- Jodi L Ford
- The Ohio State University College of Nursing, 1585 Neil Ave. Columbus, OH, 43210 614-292-6862, United States.
| | - Raymond P Stowe
- Senior Scientist, Microgen Laboratories,903 Texas Avenue, La Marque, TX, 77568, United States.
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McCully KS. Hyperhomocysteinemia, Suppressed Immunity, and Altered Oxidative Metabolism Caused by Pathogenic Microbes in Atherosclerosis and Dementia. Front Aging Neurosci 2017; 9:324. [PMID: 29056905 PMCID: PMC5635055 DOI: 10.3389/fnagi.2017.00324] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 09/20/2017] [Indexed: 12/19/2022] Open
Abstract
Many pathogenic microorganisms have been demonstrated in atherosclerotic plaques and in cerebral plaques in dementia. Hyperhomocysteinemia, which is a risk factor for atherosclerosis and dementia, is caused by dysregulation of methionine metabolism secondary to deficiency of the allosteric regulator, adenosyl methionine. Deficiency of adenosyl methionine results from increased polyamine biosynthesis by infected host cells, causing increased activity of ornithine decarboxylase, decreased nitric oxide and peroxynitrate formation and impaired immune reactions. The down-regulation of oxidative phosphorylation that is observed in aging and dementia is attributed to deficiency of thioretinaco ozonide oxygen complexed with nicotinamide adenine dinucleotide and phosphate, which catalyzes oxidative phosphorylation. Adenosyl methionine biosynthesis is dependent upon thioretinaco ozonide and adenosine triphosphate (ATP), and the deficiency of adenosyl methionine and impaired immune function in aging are attributed to depletion of thioretinaco ozonide from mitochondrial membranes. Allyl sulfides and furanonaphthoquinones protect against oxidative stress and apoptosis by increasing the endogenous production of hydrogen sulfide and by inhibiting electron transfer to the active site of oxidative phosphorylation. Diallyl trisulfide and napabucasin inhibit the signaling by the signal transducer and activator of transcription 3 (Stat3), potentially enhancing immune function by effects on T helper lymphocytes and promotion of apoptosis. Homocysteine promotes endothelial dysfunction and apoptosis by the unfolded protein response and endoplasmic reticulum stress through activation of the N-methyl D-aspartate (NMDA) receptor, causing oxidative stress, calcium influx, apoptosis and endothelial dysfunction. The prevention of atherosclerosis and dementia may be accomplished by a proposed nutritional metabolic homocysteine-lowering protocol which enhances immunity and corrects the altered oxidative metabolism in atherosclerosis and dementia.
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Affiliation(s)
- Kilmer S. McCully
- Pathology, VA Boston Healthcare System (VHA), Boston, MA, United States
- Pathology, Harvard Medical School, Boston, MA, United States
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20
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Peterson MR, Haller SE, Ren J, Nair S, He G. CARD9 as a potential target in cardiovascular disease. Drug Des Devel Ther 2016; 10:3799-3804. [PMID: 27920495 PMCID: PMC5125811 DOI: 10.2147/dddt.s122508] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Systemic inflammation and localized macrophage infiltration have been implicated in cardiovascular pathologies, including coronary artery disease, carotid atherosclerosis, heart failure, obesity-associated heart dysfunction, and cardiac fibrosis. Inflammation induces macrophage infiltration and activation and release of cytokines and chemokines, causing tissue dysfunction by instigating a positive feedback loop that further propagates inflammation. Cytosolic adaptor caspase recruitment domain family, member 9 (CARD9) is a protein expressed primarily by dendritic cells, neutrophils, and macrophages, in which it mediates cytokine secretion. The purpose of this review is to highlight the role of CARD9 as a potential target in inflammation-related cardiovascular pathologies.
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Affiliation(s)
- Matthew R Peterson
- School of Pharmacy, University of Wyoming, College of Health Sciences, Laramie, WY, USA
| | - Samantha E Haller
- School of Pharmacy, University of Wyoming, College of Health Sciences, Laramie, WY, USA
| | - Jun Ren
- School of Pharmacy, University of Wyoming, College of Health Sciences, Laramie, WY, USA
| | - Sreejayan Nair
- School of Pharmacy, University of Wyoming, College of Health Sciences, Laramie, WY, USA
| | - Guanglong He
- School of Pharmacy, University of Wyoming, College of Health Sciences, Laramie, WY, USA
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21
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Qanitha A, de Mol BA, Pabittei DR, Mappangara I, van der Graaf Y, Dalmeijer GW, Burgner DP, Uiterwaal CS. Infections in early life and premature acute coronary syndrome: A case-control study. Eur J Prev Cardiol 2016; 23:1640-8. [PMID: 27006417 DOI: 10.1177/2047487316640656] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Accepted: 03/03/2016] [Indexed: 11/16/2022]
Abstract
BACKGROUND Infections in young children may affect the vasculature and initiate early atherosclerosis. Whether infections experienced in childhood play a part in adult clinical cardiovascular disease remains unclear. We investigated the association between infections in early life and the occurrence of premature coronary heart disease. METHODS We conducted a population-based case-control study of 153 patients with a first acute coronary syndrome before the age of 56 years and 153 age- and sex-matched controls. Any history of severe infections in childhood and adolescence was obtained, together with clinical and laboratory measurements and other cardiovascular risk factors. We developed an infection score for the overall burden of early life infections. Conditional logistic regression was used to assess the associations. RESULTS Infections experienced in early life increased the risk of acquiring acute coronary syndrome at a young age with an odds ratio (OR) of 2.67 (95% confidence interval (CI) 1.47-4.83, p = 0.001). After adjustments for traditional risk factors, lifestyle, dietary patterns, socio-economic status and parental history of cardiovascular events, these associations remained significant and changed only slightly. There was an indication for an interaction between infections in early life and current cardiovascular risk (Framingham Risk Score (FRS); p-interaction = 0.052). Within participants with a low FRS (<10%), the OR of early life infection for acute coronary syndrome was 1.49 (95% CI 0.72-3.08, p = 0.283); within participants with an intermediate FRS (10-20%), the OR was 4.35 (95% CI 1.60-11.84, p = 0.004); and within participants with a high FRS (>20%), the OR 10.00 (95% CI 1.21-82.51, p = 0.032). CONCLUSION Infections in early life may partly explain premature coronary heart disease in adulthood and may potentiate traditional cardiovascular risk factor effects.
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Affiliation(s)
- Andriany Qanitha
- Department of Cardio-thoracic Surgery, Academic Medical Centre, University of Amsterdam, the Netherlands Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, the Netherlands Faculty of Medicine, University of Hasanuddin, Makassar, Indonesia
| | - Bastianus Ajm de Mol
- Department of Cardio-thoracic Surgery, Academic Medical Centre, University of Amsterdam, the Netherlands
| | - Dara R Pabittei
- Department of Cardio-thoracic Surgery, Academic Medical Centre, University of Amsterdam, the Netherlands Faculty of Medicine, University of Hasanuddin, Makassar, Indonesia
| | - Idar Mappangara
- Faculty of Medicine, University of Hasanuddin, Makassar, Indonesia
| | - Yolanda van der Graaf
- Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, the Netherlands
| | - Geertje W Dalmeijer
- Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, the Netherlands
| | - David P Burgner
- Department of Paediatrics, University of Melbourne, Australia
| | - Cuno Spm Uiterwaal
- Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, the Netherlands
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22
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Allen S, Liu YG, Scott E. Engineering nanomaterials to address cell-mediated inflammation in atherosclerosis. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2016; 2:37-50. [PMID: 27135051 DOI: 10.1007/s40883-016-0012-9] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Atherosclerosis is an inflammatory disorder with a pathophysiology driven by both innate and adaptive immunity and a primary cause of cardiovascular disease (CVD) worldwide. Vascular inflammation and accumulation of foam cells and their products induce maturation of atheromas, or plaques, which can rupture by metalloprotease action, leading to ischemic stroke or myocardial infarction. Diverse immune cell populations participate in all stages of plaque maturation, many of which directly influence plaque stability and rupture via inflammatory mechanisms. Current clinical treatments for atherosclerosis focus on lowering serum levels of low-density lipoprotein (LDL) using therapeutics such as statins, administration of antithrombotic drugs, and surgical intervention. Strategies that address cell-mediated inflammation are lacking, and consequently have recently become an area of considerable research focus. Nanomaterials have emerged as highly advantageous tools for these studies, as they can be engineered to target specific inflammatory cell populations, deliver therapeutics of wide-ranging solubilities and enhance analytical methods that include imaging and proteomics. Furthermore, the highly phagocytic nature of antigen presenting cells (APCs), a diverse cell population central to the initiation of immune responses and inflammation, make them particularly amenable to targeting and modulation by nanoscale particulates. Nanomaterials have therefore become essential components of vaccine formulations and treatments for inflammation-driven pathologies like autoimmunity, and present novel opportunities for immunotherapeutic treatments of CVD. Here, we review recent progress in the design and use of nanomaterials for therapeutic assessment and treatment of atherosclerosis. We will focus on promising new approaches that utilize nanomaterials for cell-specific imaging, gene therapy and immunomodulation.
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Affiliation(s)
- Sean Allen
- Department of Biomedical Engineering, Northwestern University, Evanston IL, USA
| | - Yu-Gang Liu
- Department of Biomedical Engineering, Northwestern University, Evanston IL, USA
| | - Evan Scott
- Department of Biomedical Engineering, Northwestern University, Evanston IL, USA
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Matusiak A, Chałubiński M, Broncel M, Rechciński T, Rudnicka K, Miszczyk E, Walencka M, Strapagiel D, Gajewski A, Chmiela M. Putative consequences of exposure to Helicobacter pylori infection in patients with coronary heart disease in terms of humoral immune response and inflammation. Arch Med Sci 2016; 12:45-54. [PMID: 26925118 PMCID: PMC4754360 DOI: 10.5114/aoms.2015.50772] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Accepted: 06/03/2014] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Pathogens, including Helicobacter pylori (Hp), have been suggested to contribute to the development of coronary heart disease (CHD), although the evidence still remains insufficient. The study was focused on the exposure of CHD patients to Hp and resulting anti-Hp heat shock protein B HspB antibody production in relation to the level of serum lipopolysaccharide binding protein (LBP) as a marker of inflammation. MATERIAL AND METHODS One hundred seventy CHD patients and 58 non-CHD individuals participated in this study. Coronary angiography confirmed the atheromatic background of CHD. The panel of classical risk factors included: arterial hypertension, diabetes, total cholesterol, low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol, triglycerides, obesity and nicotinism. The Hp status was estimated by (13)C urea breath test and serology. Immunoblot and ELISA were used for screening the sera samples for anti-Hp HspB immunoglobulins (Igs) and LBP. RESULTS Coronary heart disease patients were exposed to Hp more frequently than non-CHD individuals. This was associated with increased levels of specific anti-Hp IgG2 and IgA as well as total IgA. Hp infected CHD and non-CHD donors produced anti-Hp HspB IgG cross-reacting with human Hsp 60. In CHD patients the LBP level was significantly higher in comparison to non-CHD donors. This was related to the severity of the disease. Type I Hp strains stimulated higher LBP levels than less pathogenic type II isolates. CONCLUSIONS Lipopolysaccharide binding protein secreted in excess together with anti-Hp HspB, cross-reacting with human Hsp60, may increase the risk of vascular pathologies in Hp-exposed CHD patients.
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Affiliation(s)
- Agnieszka Matusiak
- Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - Maciej Chałubiński
- Department of Internal Diseases and Clinical Pharmacology, Biegański Regional Specialty Hospital, Medical University of Lodz, Lodz, Poland
| | - Marlena Broncel
- Department of Internal Diseases and Clinical Pharmacology, Biegański Regional Specialty Hospital, Medical University of Lodz, Lodz, Poland
| | - Tomasz Rechciński
- II Cardiology Clinic, Bieganski Regional Specialty Hospital, Medical University of Lodz, Lodz, Poland
| | - Karolina Rudnicka
- Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - Eliza Miszczyk
- Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - Maria Walencka
- Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - Dominik Strapagiel
- Biobank Lab, Department of Molecular Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - Adrian Gajewski
- Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - Magdalena Chmiela
- Laboratory of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
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Abstract
The role of infection in cerebrovascular disease is complex and remains incompletely understood. Over the last 5 years, investigators have made notable inroads in untangling this thorny topic. In this review, we examine these recent developments, concentrating on four aspects of the relationship between infection and stroke. We first discuss specific infectious agents as direct causes of stroke, focusing on recent work implicating herpesviruses and HIV in cerebral vasculopathy. We then discuss systemic infection of any type as a stroke trigger, focusing on the relationship of infection to timing of acute stroke, both in children and adults, as well as the role of vaccination in stroke prevention. We examine the evidence for chronic infection or "infectious burden" as a stroke risk factor. Finally, we discuss recent work on infection as a risk factor for increased morbidity after stroke, possible mechanisms mediating this effect, and the evidence for prophylactic antibiotics.
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Affiliation(s)
- Eliza C Miller
- The Neurological Institute of New York, 710 W. 168th St., 14th floor, New York, NY, 10032, USA.
| | - Mitchell S V Elkind
- The Neurological Institute of New York, 710W. 168th St., Room 642, New York, NY, 10032, USA.
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25
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McCully KS. Homocysteine Metabolism, Atherosclerosis, and Diseases of Aging. Compr Physiol 2015; 6:471-505. [DOI: 10.1002/cphy.c150021] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Dratva J, Caviezel S, Schaffner E, Bettschart R, Kuenzli N, Schindler C, Schmidt-Trucksäss A, Stolz D, Zemp E, Probst-Hensch N. Infectious diseases are associated with carotid intima media thickness in adolescence. Atherosclerosis 2015; 243:609-15. [PMID: 26545015 DOI: 10.1016/j.atherosclerosis.2015.10.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Revised: 10/04/2015] [Accepted: 10/17/2015] [Indexed: 01/28/2023]
Abstract
OBJECTIVE Inflammatory risk factors in childhood, e.g. obesity, impact on carotid artery intima media thickness (CIMT), an early indicator of atherosclerosis. Little is known on potential infectious origins in childhood. We investigated the association between number of reported different childhood infectious diseases and CIMT in adolescence. STUDY DESIGN 288 SAPALDIA offspring (8-21years) underwent a clinical examination in 2010-2011: anthropometry, blood pressure, CIMT, blood draw (cardiovascular biomarkers, cotinine). Offspring and parents gave information on individuals' and family health, child's vaccination status, infectious diseases and other early life factors. Life-time prevalence of bronchitis, pneumonia, tonsillitis, otitis, mononucleosis, meningitis, appendicitis, and scarlet fever were investigated, separately, and as cumulative infectious disease score. Multilevel adjusted linear regression analysis on the association between subjects' CIMT average and infectious diseases score was performed, stratifying by sex. RESULTS Youth (mean age 14.8 yrs; 53% female) reported on average 1.3 of the listed infectious diseases; 22% boys and 15% girls reported ≥3 infectious diseases (p = 0.136). Two-thirds were vaccinated according to recommendations (boys 56%, girls 61.5%, p = 0.567). Sex-stratified analyses yielded significantly increased CIMT in boys with ≥3 infectious diseases vs. none (0.046 mm, 95%CI 0.024; 0.068). In girls, the effect was of same direction but statistically non-significant (0.011 mm, 95%CI -0.015; 0.036). CONCLUSION The SAPALDIA Youth study complements current evidence on infectious origins of atherosclerosis in adults. The larger effects observed in boys may relate to a higher vulnerability of the vasculature and/or to infectious pathogens. Our data are suggestive of an early impact of childhood infectious diseases on vascular health.
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Affiliation(s)
- Julia Dratva
- Swiss Tropical and Public Health Institute, Basel, CH, Socinstrasse 57, CH-4002 Basel, Switzerland; University of Basel, CH, Petersplatz 1, CH-4031 Basel, Switzerland.
| | - Seraina Caviezel
- Swiss Tropical and Public Health Institute, Basel, CH, Socinstrasse 57, CH-4002 Basel, Switzerland; University of Basel, CH, Petersplatz 1, CH-4031 Basel, Switzerland; Department for Sport, Exercise and Health, Division Sports and Exercise Medicine, University of Basel, St. Jakob-Arena, Brüglingen 33, CH-4052 Basel, Switzerland
| | - Emmanuel Schaffner
- Swiss Tropical and Public Health Institute, Basel, CH, Socinstrasse 57, CH-4002 Basel, Switzerland; University of Basel, CH, Petersplatz 1, CH-4031 Basel, Switzerland
| | - Robert Bettschart
- Lungenpraxis Hirslanden Klinik Aarau, Schanzweg 7, CH-5000 Aarau, Switzerland
| | - Nino Kuenzli
- Swiss Tropical and Public Health Institute, Basel, CH, Socinstrasse 57, CH-4002 Basel, Switzerland; University of Basel, CH, Petersplatz 1, CH-4031 Basel, Switzerland
| | - Christian Schindler
- Swiss Tropical and Public Health Institute, Basel, CH, Socinstrasse 57, CH-4002 Basel, Switzerland; University of Basel, CH, Petersplatz 1, CH-4031 Basel, Switzerland
| | - Arno Schmidt-Trucksäss
- Department for Sport, Exercise and Health, Division Sports and Exercise Medicine, University of Basel, St. Jakob-Arena, Brüglingen 33, CH-4052 Basel, Switzerland
| | - Daiana Stolz
- Universitätsspital, Pneumologie, Basel CH, Petersgraben 4, CH-4031 Basel, Switzerland
| | - Elisabeth Zemp
- Swiss Tropical and Public Health Institute, Basel, CH, Socinstrasse 57, CH-4002 Basel, Switzerland; University of Basel, CH, Petersplatz 1, CH-4031 Basel, Switzerland
| | - Nicole Probst-Hensch
- Swiss Tropical and Public Health Institute, Basel, CH, Socinstrasse 57, CH-4002 Basel, Switzerland; University of Basel, CH, Petersplatz 1, CH-4031 Basel, Switzerland
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Seo KW, Lee SJ, Ye BH, Kim YW, Bae SS, Kim CD. Mechanical stretch enhances the expression and activity of osteopontin and MMP-2 via the Akt1/AP-1 pathways in VSMC. J Mol Cell Cardiol 2015; 85:13-24. [DOI: 10.1016/j.yjmcc.2015.05.006] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Revised: 05/06/2015] [Accepted: 05/10/2015] [Indexed: 01/02/2023]
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Jeong SJ, Ku NS, Han SH, Choi JY, Kim CO, Song YG, Kim JM. Anti-cytomegalovirus antibody levels are associated with carotid atherosclerosis and inflammatory cytokine production in elderly Koreans. Clin Chim Acta 2015; 445:65-9. [DOI: 10.1016/j.cca.2015.03.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2014] [Revised: 02/24/2015] [Accepted: 03/02/2015] [Indexed: 01/04/2023]
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Vijayvergiya R, Vadivelu R. Role of Helicobacter pylori infection in pathogenesis of atherosclerosis. World J Cardiol 2015; 7:134-143. [PMID: 25810813 PMCID: PMC4365310 DOI: 10.4330/wjc.v7.i3.134] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 12/01/2014] [Indexed: 02/06/2023] Open
Abstract
Though a century old hypothesis, infection as a cause for atherosclerosis is still a debatable issue. Epidemiological and clinical studies had shown a possible association but inhomogeneity in the study population and study methods along with potential confounders have yielded conflicting results. Infection triggers a chronic inflammatory state which along with other mechanisms such as dyslipidemia, hyper-homocysteinemia, hypercoagulability, impaired glucose metabolism and endothelial dysfunction, contribute in pathogenesis of atherosclerosis. Studies have shown a positive relations between Cytotoxic associated gene-A positive strains of Helicobacter pylori and vascular diseases such as coronary artery disease and stroke. Infection mediated genetic modulation is a new emerging theory in this regard. Further large scale studies on infection and atherosclerosis focusing on multiple pathogenetic mechanisms may help in refining our knowledge in this aspect.
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Budzyński J, Wiśniewska J, Ciecierski M, Kędzia A. Association between Bacterial Infection and Peripheral Vascular Disease: A Review. Int J Angiol 2015; 25:3-13. [PMID: 26900306 DOI: 10.1055/s-0035-1547385] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
There are an increasing number of data showing a clinically important association between bacterial infection and peripheral artery disease (PAD). Bacteria suspected of being involved in PAD pathogenesis are: periodontal bacteria, gut microbiota, Helicobacter pylori, and Chlamydia pneumoniae. Infectious agents may be involved in the pathogenesis of atherosclerosis via activation of a systemic or local host immunological response to contamination of extravascular tissues or the vascular wall, respectively. A systemic immunological reaction may damage vascular walls in the course of autoimmunological cross-reactions between anti-pathogen antibodies and host vascular antigens (immunological mimicry), pathogen burden mechanisms (nonspecific activation of inflammatory processes in the vascular wall), and neuroendocrine-immune cross-talk. Besides activating the inflammatory pathway, bacterial infection may trigger PAD progression or exacerbation by enhancement of platelet reactivity, by a stimulatory effect on von Willebrand factor binding, factor VIII, fibrinogen, P-selectin activation, disturbances in plasma lipids, increase in oxidative stress, and resistance to insulin. Local inflammatory host reaction and induction of atherosclerotic plaque progression and/or instability result mainly from atherosclerotic plaque colonization by microorganisms. Despite these premises, the role of bacterial infection in PAD pathogenesis should still be recognized as controversial, and randomized, controlled trials are required to evaluate the outcome of periodontal or gut bacteria modification (through diet, prebiotics, and probiotics) or eradication (using antibiotics) in hard and surrogate cardiovascular endpoints.
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Affiliation(s)
- Jacek Budzyński
- Chair of Vascular and Internal Diseases, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland; Department of Vascular and Internal Diseases, Jan Biziel Hospital No. 2, Bydgoszcz, Poland
| | - Joanna Wiśniewska
- Department of Vascular and Internal Diseases, Jan Biziel Hospital No. 2, Bydgoszcz, Poland
| | - Marek Ciecierski
- Department of Vascular and Internal Diseases, Jan Biziel Hospital No. 2, Bydgoszcz, Poland
| | - Anna Kędzia
- Department of Oral Microbiology, Chair of Microbiology, Medical University, Gdańsk, Poland
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31
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Willeit P, Thompson SG, Agewall S, Bergström G, Bickel H, Catapano AL, Chien KL, de Groot E, Empana JP, Etgen T, Franco OH, Iglseder B, Johnsen SH, Kavousi M, Lind L, Liu J, Mathiesen EB, Norata GD, Olsen MH, Papagianni A, Poppert H, Price JF, Sacco RL, Yanez DN, Zhao D, Schminke U, Bülbül A, Polak JF, Sitzer M, Hofman A, Grigore L, Dörr M, Su TC, Ducimetière P, Xie W, Ronkainen K, Kiechl S, Rundek T, Robertson C, Fagerberg B, Bokemark L, Steinmetz H, Ikram MA, Völzke H, Lin HJ, Plichart M, Tuomainen TP, Desvarieux M, McLachlan S, Schmidt C, Kauhanen J, Willeit J, Lorenz MW, Sander D. Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration. Eur J Prev Cardiol 2014; 23:194-205. [PMID: 25416041 DOI: 10.1177/2047487314560664] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Accepted: 10/31/2014] [Indexed: 01/09/2023]
Abstract
BACKGROUND Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population. METHODS Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses. RESULTS Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). 'Inflammatory load', defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest 'inflammatory load' had a greater CCA-IMT progression (p = 0.015). CONCLUSION Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis.
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Affiliation(s)
- Peter Willeit
- The Department of Public Health and Primary Care, University of Cambridge, UK Department of Neurology, Medical University Innsbruck, Austria
| | - Simon G Thompson
- The Department of Public Health and Primary Care, University of Cambridge, UK
| | - Stefan Agewall
- Institute of Clinical Sciences, University of Oslo, and the Department of Cardiology, Oslo University Hospital Ullevål, Norway
| | - Göran Bergström
- Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden
| | - Horst Bickel
- Department of Psychiatry and Psychotherapy, University Hospital of the Technische Universität München, Germany
| | - Alberico L Catapano
- Department of Pharmacological Sciences, University of Milan, and IRCSS Multimedica Sesto S Giovanni, Milan, Italy
| | - Kuo-Liong Chien
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
| | - Eric de Groot
- Academic Medical Centre, Cardiology and Thoracic Surgery, and Imagelabonline and Cardiovascular, Amsterdam, The Netherlands
| | | | - Thorleif Etgen
- Department of Neurology, Kliniken Südostbayern, Klinikum Traunstein, Germany
| | - Oscar H Franco
- Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Bernhard Iglseder
- Department of Geriatric Medicine, Paracelsus Medical University, and the Gemeinnützige Salzburger Landeskliniken Betriebsgesellschaft GmbH, Christian-Doppler-Klinik, Salzburg, Austria
| | - Stein H Johnsen
- Department of Neurology and Neurophysiology, University Hospital of Northern Norway, and the Department of Clinical Medicine, University of Tromsø, Tromsø, Norway
| | - Maryam Kavousi
- Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Lars Lind
- Department of Medicine, Uppsala University, Sweden
| | - Jing Liu
- Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, PR China
| | - Ellisiv B Mathiesen
- Department of Neurology and Neurophysiology, University Hospital of Northern Norway, and the Department of Clinical Medicine, University of Tromsø, Tromsø, Norway
| | - Giuseppe D Norata
- Department of Pharmacological Sciences, University of Milan, and the SISA Centre for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy
| | - Michael H Olsen
- Department of Endocrinology, Centre for Individualized Medicine in Arterial Diseases, Odense University Hospital, Denmark
| | - Aikaterini Papagianni
- Department of Nephrology, Aristotle University of Thessaloniki, Hippokration General Hospital, Greece
| | - Holger Poppert
- Department of Neurology, University Hospital of the Technische Universität München, Germany
| | - Jackie F Price
- Centre for Population Health Sciences, University of Edinburgh, UK
| | - Ralph L Sacco
- Department of Neurology, Miller School of Medicine, University of Miami, FL, USA
| | - David N Yanez
- Department of Biostatistics, University of Washington, Seattle, WA, USA
| | - Dong Zhao
- Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, PR China
| | - Ulf Schminke
- Department of Neurology, Greifswald University Clinic, Germany
| | - Alpaslan Bülbül
- Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Joseph F Polak
- Tufts University School of Medicine, Tufts Medical Center, Boston, MA, USA
| | - Matthias Sitzer
- Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany Department of Neurology, Klinikum Herford, Germany
| | - Albert Hofman
- Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
| | - Liliana Grigore
- Department of Pharmacological Sciences, University of Milan, and the SISA Centre for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy
| | - Marcus Dörr
- Department B for Internal Medicine, University Medicine Greifswald, and the German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Germany
| | - Ta-Chen Su
- Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
| | | | - Wuxiang Xie
- Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, PR China
| | - Kimmo Ronkainen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Stefan Kiechl
- Department of Neurology, Medical University Innsbruck, Austria
| | - Tatjana Rundek
- Department of Neurology, Miller School of Medicine, University of Miami, FL, USA
| | | | - Björn Fagerberg
- Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden
| | - Lena Bokemark
- Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden
| | - Helmuth Steinmetz
- Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Henry Völzke
- Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, Greifswald, Germany
| | - Hung-Ju Lin
- Department of Internal Medicine, National Taiwan University, Taipei, Taiwan Health Management Centre, National Taiwan University Hospital, Taipei, Taiwan
| | - Matthieu Plichart
- INSERM, U970, Université Paris Descartes, France Gerontology Department, Broca Hospital, Paris, France
| | - Tomi-Pekka Tuomainen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Moise Desvarieux
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA, and the École des Hautes Études en Santé Publique, and INSERM U738, Paris, France
| | - Stela McLachlan
- Centre for Population Health Sciences, University of Edinburgh, UK
| | - Caroline Schmidt
- Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden
| | - Jussi Kauhanen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Johann Willeit
- Department of Neurology, Medical University Innsbruck, Austria
| | - Matthias W Lorenz
- Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Dirk Sander
- Department of Neurology, Benedictus Krankenhaus Tutzing and Feldafing, Tutzing, Germany and Technische Universität München, Germany
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Khoretonenko MV, Brunson JL, Senchenkov E, Leskov IL, Marks CR, Stokes KY. Platelets, acting in part via P-selectin, mediate cytomegalovirus-induced microvascular dysfunction. Am J Physiol Heart Circ Physiol 2014; 307:H1745-53. [PMID: 25326535 DOI: 10.1152/ajpheart.00201.2014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Cytomegalovirus (CMV) infects a majority of the population worldwide. It has been implicated in cardiovascular disease, induces microvascular dysfunction, and synergizes with hypercholesterolemia to promote leukocyte and platelet recruitment in venules. Although platelets and platelet-associated P-selectin contribute to cardiovascular disease inflammation, their role in CMV-induced vascular responses is unknown. We assessed the role of platelets in CMV-induced microvascular dysfunction by depleting platelets and developing bone marrow chimeric mice deficient in platelet P-selectin. Wild-type and chimeric mice received mock or murine (m)CMV intraperitoneally. Five weeks later, some mice were switched to a high-cholesterol diet (HC) to investigate the synergism between mCMV and HC. Arteriolar vasodilation and recruitment of leukocytes and donor platelets in venules were measured at 11wk. mCMV with or without HC caused significant endothelial dysfunction in arterioles. Platelet depletion restored normal vasodilation in mCMV-HC but not mCMV-ND mice, whereas protection was seen in both groups for platelet P-selectin chimeras. Only mCMV + HC elevated leukocyte and platelet recruitment in venules. Leukocyte adhesion was reduced to mock levels by acute platelet depletion but was only partially decreased in platelet P-selectin chimeras. Platelets from mCMV-HC mice and, to a lesser extent, mCMV-ND but not mock-HC mice showed significant adhesion in mCMV-HC recipients. Our findings implicate a role for platelets, acting through P-selectin, in CMV-induced arteriolar dysfunction and suggest that the addition of HC leads to a platelet-dependent, inflammatory infiltrate that is only partly platelet P-selectin dependent. CMV appeared to have a stronger activating influence than HC on platelets and may represent an additional therapeutic target in vulnerable patients.
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Affiliation(s)
- Mikhail V Khoretonenko
- Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center, Shreveport, Louisiana
| | - Jerry L Brunson
- Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center, Shreveport, Louisiana
| | - Evgeny Senchenkov
- Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana
| | - Igor L Leskov
- Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana
| | - Christian R Marks
- Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana
| | - Karen Y Stokes
- Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; and Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center, Shreveport, Louisiana
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Wu CH, Chen LS, Yen MF, Chiu YH, Fann CY, Chen HH, Pan SL. Does non-central nervous system tuberculosis increase the risk of ischemic stroke? A population-based propensity score-matched follow-up study. PLoS One 2014; 9:e98158. [PMID: 25048551 PMCID: PMC4105466 DOI: 10.1371/journal.pone.0098158] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Accepted: 04/29/2014] [Indexed: 12/02/2022] Open
Abstract
Background Previous studies on the association between tuberculosis and the risk of developing ischemic stroke have generated inconsistent results. We therefore performed a population-based, propensity score-matched longitudinal follow-up study to investigate whether contracting non-central nervous system (CNS) tuberculosis leads to an increased risk of ischemic stroke. Methods We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 5804 persons with at least three ambulatory visits in 2001 with the principal diagnosis of non-CNS tuberculosis were enrolled in the tuberculosis group. The non-tuberculosis group consisted of 5804, propensity score-matched subjects without tuberculosis. The three-year ischemic stroke-free survival rates for these 2 groups were estimated using the Kaplan-Meier method. The stratified Cox proportional hazards regression was used to estimate the effect of tuberculosis on the occurrence of ischemic stroke. Results During three-year follow-up, 176 subjects in the tuberculosis group (3.0%) and 207 in the non-tuberculosis group (3.6%) had ischemic stroke. The hazard ratio for developing ischemic stroke in the tuberculosis group was 0.92 compared to the non-tuberculosis group (95% confidence interval: 0.73–1.14, P = 0.4299). Conclusions Non-CNS tuberculosis does not increase the risk of subsequent ischemic stroke.
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Affiliation(s)
- Chueh-Hung Wu
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Li-Sheng Chen
- School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ming-Fang Yen
- School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yueh-Hsia Chiu
- Department and Graduate Institute of Health Care Management, Chang Gung University, Tao-Yuan, Taiwan
| | - Ching-Yuan Fann
- Department of Nutrition and Health Sciences, Kainan University, Tao-Yuan, Taiwan
| | - Hsiu-Hsi Chen
- Centre of Biostatistics Consultation, College of Public Health, National Taiwan University, Taipei, Taiwan
- Division of Biostatistics, Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Shin-Liang Pan
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- * E-mail:
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Sessa R, Pietro MD, Filardo S, Turriziani O. Infectious burden and atherosclerosis: A clinical issue. World J Clin Cases 2014; 2:240-249. [PMID: 25032197 PMCID: PMC4097149 DOI: 10.12998/wjcc.v2.i7.240] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 05/16/2014] [Accepted: 06/11/2014] [Indexed: 02/05/2023] Open
Abstract
Atherosclerotic cardiovascular diseases, chronic inflammatory diseases of multifactorial etiology, are the leading cause of death worldwide. In the last decade, more infectious agents, labeled as “infectious burden”, rather than any single pathogen, have been showed to contribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae (C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet aggregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule production. Others, such as Helicobacter pylori (H. pylori), influenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall (e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents (such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may contribute to atherosclerosis, defining the interplay of more infectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be amplified. Clearly, continued research and a greater awareness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis.
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Mathur J, Guthrie JD, Javed U, Sheikh MY. Evaluation of the Association between Compensated Hepatitis C Infectivity and Endothelial Dysfunction, Using Flow-Mediated Vasodilatation of the Brachial Artery. JOURNAL OF DIAGNOSTIC MEDICAL SONOGRAPHY 2014. [DOI: 10.1177/8756479314531854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background and Aim: We prospectively investigated, using sonographic methods, whether hepatitis C infection in compensated patients is related to endothelial dysfunction of the brachial artery, a potential indicator of subclinical atherosclerosis. Methods: Brachial artery flow-mediated dilatation (FMD) was used as a noninvasive test to measure the endothelial function of the brachial artery among the cases and the controls. The peak systolic velocity (PSV) and the resistive index (RI) were also measured. Multivariate statistics were used to compare the FMD, PSV, and RI in 28 cases (diagnosed with hepatitis C) and 14 healthy controls, all of whom were without cardiovascular risk factors or a history of cardiovascular disease. Results: Flow-mediated dilatation (baseline to 1 minute post-cuff inflation) was positively correlated with the patient’s body mass index (BMI) (Pearson’s r = .309, P = .025). When the BMI was accounted for using analysis of covariance (ANCOVA), there was no evidence for a significant difference between the mean FMD of the cases versus the controls ( F = 0.11, P = .598). The mean FMD was 6.6% (95% confidence interval [CI], 3.1%-10.2%) among the cases and 7.3% (95% CI, 1.1%-13.6%) among the controls. Peak systolic velocity and RI (baseline to 3 minutes post-cuff inflation) were not positively correlated with BMI. The mean PSV was 0.57 m/s (95% CI, 0.51-0.66) for the cases and 0.64 m/s (95% CI, 0.56-0.72) for the controls; repeated measures analysis of variance (ANOVA) indicated no significant difference ( F = 1.65, P = .208). Similarly, the mean RI was 0.87 (95% CI, 0.85-0.89) among the cases and 0.64 (95% CI, 0.82-0.88) among the controls, with no significant difference ( P = .772). Conclusion: Our results show that hepatitis C positivity in compensated patients, in the absence of cardiovascular risk factors, does not appear to be independently associated with endothelial dysfunction when objectively analyzed by brachial artery flow-mediated vasodilatation.
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Affiliation(s)
- Jagrati Mathur
- Division of Internal Medicine, University of California, San Francisco, Fresno, CA, USA
| | - Joy D. Guthrie
- Medical Imaging, Community Regional Medical Center, Fresno, CA, USA
| | - Usman Javed
- Medical Imaging, Community Regional Medical Center, Fresno, CA, USA
- Division of Cardiology, University of California, San Francisco, Fresno, CA, USA
| | - Muhammad Y. Sheikh
- Division of Gastroenterology, University of California, San Francisco, Fresno, CA, USA
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Jabłońska A, Paradowska E, Studzińska M, Suski P, Nowakowska D, Wiśniewska-Ligier M, Woźniakowska-Gęsicka T, Wilczyński J, Leśnikowski ZJ. Relationship between toll-like receptor 2 Arg677Trp and Arg753Gln and toll-like receptor 4 Asp299Gly polymorphisms and cytomegalovirus infection. Int J Infect Dis 2014; 25:11-5. [PMID: 24813591 DOI: 10.1016/j.ijid.2014.04.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 04/15/2014] [Accepted: 04/16/2014] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVES The association among specific single-nucleotide polymorphisms (SNPs) in TLR2 (Arg677Trp, Arg753Gln) and TLR4 (Asp299Gln) and human cytomegalovirus (CMV) infection was studied in infants and adults. METHODS The TLR2 and TLR4 polymorphisms were genotyped in 151 patients with CMV infections and in 78 unrelated healthy individuals. Genotyping was performed by restriction fragment length polymorphism (RFLP) analysis of PCR-amplified fragments. The viral load was measured by quantitative real-time PCR. RESULTS Almost all of the patients with CMV infections were wild-type homozygotes without TLR2 and TLR4 polymorphisms. No significant differences in TLR2 and TLR4 polymorphisms were observed between infants with or without CMV infection. Compared with adults with CMV infections, heterozygosity for the TLR2 Arg677Trp and TLR4 Asp299Gly SNPs was detected more frequently in healthy individuals (p<0.05). Logistic regression analysis showed that the wild-type TLR2 genotype was associated with an increased risk of CMV infection and that heterozygosity for TLR2 and TLR4 SNPs diminished the risk of CMV infection in adult patients. An association between CMV load and the TLR4 SNP was found. CONCLUSION Our results suggest that the wild-type TLR2 genotype may be a risk factor for CMV replication in adult patients.
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Affiliation(s)
- Agnieszka Jabłońska
- Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland
| | - Edyta Paradowska
- Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland.
| | - Mirosława Studzińska
- Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland
| | - Patrycja Suski
- Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland
| | - Dorota Nowakowska
- Department of Foetal-Maternal Medicine and Gynaecology, Third Chair of Gynaecology and Obstetrics, Medical University, Lodz, Poland; Department of Foetal-Maternal Medicine and Gynaecology, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland
| | | | | | - Jan Wilczyński
- Department of Foetal-Maternal Medicine and Gynaecology, Third Chair of Gynaecology and Obstetrics, Medical University, Lodz, Poland; Department of Foetal-Maternal Medicine and Gynaecology, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland
| | - Zbigniew J Leśnikowski
- Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St., 93-232 Lodz, Poland
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Vespasiani-Gentilucci U, Gallo P, Vincentis AD, Galati G, Picardi A. Hepatitis C virus and metabolic disorder interactions towards liver damage and atherosclerosis. World J Gastroenterol 2014; 20:2825-2838. [PMID: 24659875 PMCID: PMC3961987 DOI: 10.3748/wjg.v20.i11.2825] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/25/2013] [Accepted: 01/03/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide, and alterations of glucose metabolism have reached pandemic proportions in western countries. However, the frequent coexistence between these two conditions is more than simply coincidental, since HCV can induce insulin resistance through several mechanisms. Indeed, the virus interferes with insulin signaling both directly and indirectly, inducing the production of pro-inflammatory cytokines. Furthermore, the entire viral life cycle has strict interconnections with lipid metabolism, and HCV is responsible for a "viral" steatosis which is frequently superimposed to a "metabolic" one. Several evidences suggest that HCV-induced metabolic disorders contribute both to the evolution of liver fibrosis and, likely, to the progression of the other disorders which are typically associated with altered metabolism, in particular atherosclerosis. In the present review, we will examine in depth the links between HCV infection and insulin resistance, liver steatosis and diabetes, and analyze the impact of these interactions on the progression of liver fibrosis and atherosclerosis. Special attention will be focused on the highly debated topic of the relationship between HCV infection and cardiovascular disease. The available clinical literature on this item will be broadly reviewed and all the mechanisms possibly implied will be discussed.
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Abstract
UNLABELLED Nosocomial and ventilator associated pneumonias that plague critically ill, elderly and long-term care residents could be reduced with effective oral hygiene practices facilitated collaboratively between nurses and dental hygienists. BACKGROUND Nosocomial pneumonias, specifically aspiration pneumonias and ventilator-associated pneumonias in the elderly and infirm have become a major health care issue, The provision of oral care in hospital and hospital-like facilities presents challenges that can prevent patients from receiving optimal oral care One sequela can be aspiration pneumonia which ranks first in mortality and second in morbidity among all nosocomial infections. Since aspiration pneumonia is linked to the colonization of oral bacteria in dental plaque and biofilm, it is time to look for creative solutions to integrating the expertise of dental hygienists into health care teams in these institutional settings. METHODS A comprehensive review of the literature was conducted regarding the etiology and prevalence of health care related pneumonias. Evidence describing the challenges and barriers that the nurses, nursing staff, and dental hygienists face in the provision of oral care in hospitals and long-term care facilities is provided. Intercollaborative solutions to providing optimal oral care in hospitals and long-term care facilities are suggested. CONCLUSION Dental hygienists have the expertise and practice experience to provide oral care in hospitals, long-term care and residential facilities. They can contribute to solving oral care challenges through intercollaboration with other health care team members. Yet, there are long-standing systemic barriers that must be addressed in order to provide this optimal care. Dental hygienists becoming better assimilated within the total health care team in hospital and residential facilities can positively impact the suffering, morbidity and mortality associated with aspiration pneumonias.
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Affiliation(s)
- Caren M Barnes
- Applied and Clinical Research, Department of Dental Hygiene, Nebraska Center for Materials and Nanoscience, University of Nebraska Medical Center, College of Dentistry, Lincoln, NE 68583-0740, USA.
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Abstract
Although human cytomegalovirus (HCMV) primary infection is generally asymptomatic, in immune-compromised patients HCMV increases morbidity and mortality. As a member of the betaherpesvirus family, in vivo studies of HCMV are limited due to its species specificity. CMVs from other species are often used as surrogates to express HCMV genes/proteins or used as models for inferring HCMV protein function in humans. Using innovative experiments, these animal models have answered important questions about CMV's life cycle, dissemination, pathogenesis, immune evasion, and host immune response. This chapter provides CMV biologists with an overview of the insights gained using these animal models. Subsequent chapters will provide details of the specifics of the experimental methods developed for each of the animal models discussed here.
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Affiliation(s)
- Pranay Dogra
- Department of Microbiology, University of Tennessee, Knoxville, TN, USA
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Martínez-Rodríguez JE, Munné-Collado J, Rasal R, Cuadrado E, Roig L, Ois A, Muntasell A, Baro T, Alameda F, Roquer J, López-Botet M. Expansion of the NKG2C+ natural killer-cell subset is associated with high-risk carotid atherosclerotic plaques in seropositive patients for human cytomegalovirus. Arterioscler Thromb Vasc Biol 2013; 33:2653-9. [PMID: 23968979 DOI: 10.1161/atvbaha.113.302163] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE Human cytomegalovirus (HCMV), a pathogen involved in the development and progression of atherosclerosis, promotes in some individuals a marked reconfiguration of the natural killer (NK)-cell compartment whose hallmark is a persistent expansion of a peripheral blood NK-cell subset expressing the CD94/NKG2C NK receptor. We aimed to evaluate whether the HCMV-associated NK-cell compartment reconfiguration is related to carotid atherosclerotic plaque (CAP) instability. APPROACH AND RESULTS NK receptor expression (ie, LILRB1, NKG2A, NKG2C, and killer immunoglobulin-like receptors [KIR]) by peripheral NK and T cells was evaluated in 40 patients with HCMV+ with CAP, including nonatherosclerotic strokes (n=15) and healthy subjects (n=11) as controls. High-risk CAP (n=16), defined as carotid stenosis >50% with ipsilateral neurological symptomatology in the previous 180 days, compared with non-high-risk CAP had higher %NKG2C+ NK cells (29.5 ± 22.4% versus 16.3 ± 13.2%; P=0.026; odds ratio, 1.053; 95% confidence interval, 1.002-1.106; P=0.042), with a corresponding reduction in the NKG2A+ NK subset (31.7 ± 17.8% versus 41.8 ± 15.8%; P=0.072). The proportions of NKG2C+ NK cells in high-risk CAP were inversely correlated with the CD4+/CD8+ ratio (R(Spearman)=-0.629; P=0.009) and directly with high-sensitivity C-reactive protein levels (R(Pearson) = 0.591; P=0.012), consistent with higher subclinical systemic inflammation. The intraplaque inflammatory infiltrate, evaluated in 27 CAP obtained after endarterectomy, showed a higher presence of subintimal CD3+ lymphocytes in those patients with HCMV-induced changes in the peripheral NK- and T-cell compartments. CONCLUSIONS The expansion of NKG2C+ NK cells in patients with CAP seems to be associated with an increased risk of plaque destabilization in some patients with chronic HCMV infection.
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Affiliation(s)
- Jose Enrique Martínez-Rodríguez
- From the Neurology Service (J.E.M.-R., R.R., E.C., A.O., J.R.) and Immunology Unit (A.M., M.L.-B.), Hospital del Mar Medical Research Institute (IMIM), Universitat Pompeu Fabra, Barcelona, Spain; and Department of Pathology (J.M.-C., T.B., F.A.) and Vascular Surgery Department (L.R.), Hospital del Mar, Universidad Autónoma de Barcelona, Barcelona, Spain
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Rubicz R, Zhu J, Laston S, Cole SA, Voruganti VS, Ebbesson SOE, Howard BV, Maccluer JW, Davidson M, Umans JG, Comuzzie AG, Göring HHH. Statistical genetic analysis of serological measures of common, chronic infections in Alaska Native participants in the GOCADAN study. Genet Epidemiol 2013; 37:751-7. [PMID: 23798484 DOI: 10.1002/gepi.21745] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Revised: 05/06/2013] [Accepted: 05/29/2013] [Indexed: 11/09/2022]
Abstract
This paper describes genetic investigations of seroreactivity to five common infectious pathogens in the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Antibody titers and seroprevalence were available for 495 to 782 (depending on the phenotype) family members at two time points, approximately 15 years apart, for Chlamydophila pneumoniae, Helicobacter pylori, cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and herpes simplex virus 2 (HSV-2). Seroprevalence rates indicate that infections with most of these pathogens are common (≥20% for all of them, >80% for H. pylori, CMV, and HSV-1). Seropositive individuals typically remain seropositive over time, with seroreversion rates of <1% to 10% over ∼15 years. Antibody titers were significantly heritable for most pathogens, with the highest estimate being 0.61 for C. pneumoniae. Significant genome-wide linkage evidence was obtained for C. pneumoniae on chromosome 15 (logarithm of odds, LOD score of 3.13). These results demonstrate that individual host genetic differences influence antibody measures of common infections in this population, and further investigation may elucidate the underlying immunological processes and genes involved.
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Affiliation(s)
- Rohina Rubicz
- Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas
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Bzowska M, Nogieć A, Skrzeczyńska-Moncznik J, Mickowska B, Guzik K, Pryjma J. Oxidized LDLs inhibit TLR-induced IL-10 production by monocytes: a new aspect of pathogen-accelerated atherosclerosis. Inflammation 2013; 35:1567-84. [PMID: 22556042 PMCID: PMC3397235 DOI: 10.1007/s10753-012-9472-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
It is widely accepted that oxidized low-density lipoproteins and local infections or endotoxins in circulation contribute to chronic inflammatory process at all stages of atherosclerosis. The hallmark cells of atherosclerotic lesions-monocytes and macrophages-are able to detect and integrate complex signals derived from lipoproteins and pathogens, and respond with a spectrum of immunoregulatory cytokines. In this study, we show strong inhibitory effect of oxLDLs on anti-inflammatory interleukin-10 production by monocytes responding to TLR2 and TLR4 ligands. In contrast, pro-inflammatory tumor necrosis factor secretion was even slightly increased, when stimulated with lipopolysaccharide from Porphyromonas gingivalis-an oral pathogen associated with atherosclerosis. The oxLDLs modulatory activity may be explained by altered recognition of pathogen-associated molecular patterns, which involves serum proteins, particularly vitronectin. We also suggest an interaction between vitronectin receptor, CD11b, and TLR2. The presented data support a novel pathway for pathogen-accelerated atherosclerosis, which relies on oxidized low-density lipoprotein-mediated modulation of anti-inflammatory response to TLR ligands.
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Affiliation(s)
- Małgorzata Bzowska
- Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland
| | - Anna Nogieć
- Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland
| | - Joanna Skrzeczyńska-Moncznik
- Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland
| | - Barbara Mickowska
- Malopolska Centre of Food Monitoring and Certification, Faculty of Food Technology, Agricultural University, Balicka 122, 30-149 Kraków, Poland
| | - Krzysztof Guzik
- Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland
| | - Juliusz Pryjma
- Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland
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Oxidized LDLs inhibit TLR-induced IL-10 production by monocytes: a new aspect of pathogen-accelerated atherosclerosis. Inflammation 2013. [PMID: 22556042 DOI: 10.1007/s110753-012-9472-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
It is widely accepted that oxidized low-density lipoproteins and local infections or endotoxins in circulation contribute to chronic inflammatory process at all stages of atherosclerosis. The hallmark cells of atherosclerotic lesions-monocytes and macrophages-are able to detect and integrate complex signals derived from lipoproteins and pathogens, and respond with a spectrum of immunoregulatory cytokines. In this study, we show strong inhibitory effect of oxLDLs on anti-inflammatory interleukin-10 production by monocytes responding to TLR2 and TLR4 ligands. In contrast, pro-inflammatory tumor necrosis factor secretion was even slightly increased, when stimulated with lipopolysaccharide from Porphyromonas gingivalis-an oral pathogen associated with atherosclerosis. The oxLDLs modulatory activity may be explained by altered recognition of pathogen-associated molecular patterns, which involves serum proteins, particularly vitronectin. We also suggest an interaction between vitronectin receptor, CD11b, and TLR2. The presented data support a novel pathway for pathogen-accelerated atherosclerosis, which relies on oxidized low-density lipoprotein-mediated modulation of anti-inflammatory response to TLR ligands.
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Player MS, Mainous AG, Everett CJ, Diaz VA, Knoll ME, Wright RU. Chlamydia pneumoniae and progression of subclinical atherosclerosis. Eur J Prev Cardiol 2012; 21:559-65. [PMID: 23253746 DOI: 10.1177/2047487312472078] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Cross-sectional investigation between presence of antibodies and coronary artery calcification (CAC) in past studies has shown no relationship, but progression over time has not been investigated. The objective of this study was to determine the relationship between presence of Chlamydia pneumoniae antibodies and progression of CAC and ankle-brachial index (ABI). DESIGN The Multiethnic Study of Atherosclerosis (MESA) is a prospective population-based cohort of racially and ethnically diverse male and female participants recruited from six communities in the USA, age 45-84 years, free of clinical cardiovascular disease at baseline. METHODS The main outcomes were progression of mean CAC and ABI between exams 1 (2000-02) and 3 (2004-05) (median follow-up of 3.13 years) by C. pneumoniae antibody. Multivariate models adjusting for demographics, obesity, smoking, alcohol use, and physical activity were computed. RESULTS Of 2223 subjects analysed, 76% were positive for C. pneumoniae antibodies. Progression of CAC was significantly higher in the antibody-positive group (93.8 vs. 78.2 agatston units, p = 0.02) and in antibody-positive subjects with CAC ≥10 at baseline (216.5 vs. 178.6, p = 0.02) than antibody-negative group. Smoking and body mass index ≥30 kg/m(2) both had interactions with presence of C. pneumoniae yielding significantly greater CAC progression. Progression of ABI did not significantly differ by C. pneumoniae antibody status in models adjusted for covariates. CONCLUSIONS C. pneumoniae antibodies are related to progression of CAC, particularly in individuals with CAC present at baseline. This provides evidence that certain groups are at higher risk of atherosclerotic progression and may be useful for risk stratification and treatment.
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Affiliation(s)
- Marty S Player
- Medical University of South Carolina, Charleston, SC, USA
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Tang-Feldman YJ, Lochhead SR, Lochhead GR, Yu C, George M, Villablanca AC, Pomeroy C. Murine cytomegalovirus (MCMV) infection upregulates P38 MAP kinase in aortas of Apo E KO mice: a molecular mechanism for MCMV-induced acceleration of atherosclerosis. J Cardiovasc Transl Res 2012. [PMID: 23192592 DOI: 10.1007/s12265-012-9428-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Multiple studies suggest an association between cytomegalovirus (CMV) infection and atherogenesis; however, the molecular mechanisms by which viral infection might exacerbate atherosclerosis are not well understood. Aortas of MCMV-infected and uninfected Apo E knockout (KO) mice were analyzed for atherosclerotic lesion development and differential gene expression. Lesions in the infected mice were larger and showed more advanced disease compared to the uninfected mice. Sixty percent of the genes in the MAPK pathway were upregulated in the infected mice. p38 and ERK 1/2 MAPK genes were 5.6- and 2.0-fold higher, respectively, in aortas of infected vs. uninfected mice. Levels of VCAM-1, ICAM-1, and MCP-1 were ~2.0-2.6-fold higher in aortas of infected vs. uninfected mice. Inhibition of p38 with SB203580 resulted in lower levels of pro-atherogenic molecules and MCMV viral load in aortas of infected mice. MCMV-induced upregulation of p38 may drive the virus-induced acceleration of atherogenesis observed in our model.
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Hechter RC, Budoff M, Hodis HN, Rinaldo CR, Jenkins FJ, Jacobson LP, Kingsley LA, Taiwo B, Post WS, Margolick JB, Detels R. Herpes simplex virus type 2 (HSV-2) as a coronary atherosclerosis risk factor in HIV-infected men: multicenter AIDS cohort study. Atherosclerosis 2012; 223:433-6. [PMID: 22472456 PMCID: PMC3392500 DOI: 10.1016/j.atherosclerosis.2012.03.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2011] [Revised: 03/03/2012] [Accepted: 03/03/2012] [Indexed: 11/19/2022]
Abstract
We assessed associations of herpes simplex virus types 1 and 2 (HSV-1 and -2), cytomegalovirus (CMV), and human herpesvirus 8 (HHV-8) infection with subclinical coronary atherosclerosis in 291 HIV-infected men in the Multicenter AIDS Cohort Study. Coronary artery calcium (CAC) was measured by non-contrast coronary CT imaging. Markers for herpesviruses infection were measured in frozen specimens collected 10-12 years prior to case identification. Multivariable logistic regression models and ordinal logistic regression models were performed. HSV-2 seropositivity was associated with coronary atherosclerosis (adjusted odds ratio [AOR]=4.12, 95% confidence interval [CI]=1.58-10.85) after adjustment for age, race/ethnicity, cardiovascular risk factors, and HIV infection related factors. Infection with a greater number of herpesviruses was associated with elevated CAC levels (AOR=1.58, 95% CI=1.06-2.36). Our findings suggest HSV-2 may be a risk factor for subclinical coronary atherosclerosis in HIV-infected men. Infection with multiple herpesviruses may contribute to the increased burden of atherosclerosis.
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Affiliation(s)
- Rulin C. Hechter
- Department of Epidemiology, UCLA School of Public Health, Box 951772, Los Angeles, CA 90095-1772
| | - Matthew Budoff
- Department of Cardiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson St, Torrance, CA 90502-2006
| | - Howard N. Hodis
- Department of Medicine and Preventive Medicine, Atherosclerosis Research Unit, Keck School of Medicine, 1975 Zonal Ave, University of Southern California, Los Angeles, CA 90089
| | - Charles R. Rinaldo
- Department of Infectious Diseases and Microbiology, Graduate School of Public Health, 130 De Soto St, University of Pittsburgh, Pittsburgh, PA 15213
| | - Frank J. Jenkins
- Department of Pathology and Infectious Diseases and Microbiology, 5117 Centre Ave, University of Pittsburgh, Pittsburgh, PA 15213
| | - Lisa P. Jacobson
- Department of Epidemiology, Bloomberg School of Public Health, 615 N. Wolfe St, Johns Hopkins University, Baltimore, MD 21205
| | - Lawrence A. Kingsley
- Department of Infectious Diseases and Microbiology, Graduate School of Public Health, 130 De Soto St, University of Pittsburgh, Pittsburgh, PA 15213
| | - Babafemi Taiwo
- Division of Infectious Diseases, Feinberg School of Medicine, 420 East Superior St, Northwestern University, Chicago, IL 60611
| | - Wendy S. Post
- Department of Epidemiology, Bloomberg School of Public Health, 615 N. Wolfe St, Johns Hopkins University, Baltimore, MD 21205
- Division of Cardiology, Department of Medicine, 615 N. Wolfe St, Johns Hopkins University, Baltimore, MD 21205
| | - Joseph B. Margolick
- Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, 615 N. Wolfe St, Johns Hopkins University, Baltimore, MD 21205
| | - Roger Detels
- Department of Epidemiology, UCLA School of Public Health, Box 951772, Los Angeles, CA 90095-1772
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Carrillo-Córdova LD, Uribe M, Méndez-Sánchez N. Atherosclerosis and chronic hepatitis C. Ann Hepatol 2012; 11:574-575. [DOI: 10.1016/s1665-2681(19)31477-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
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Paul-Clark MJ, George PM, Gatheral T, Parzych K, Wright WR, Crawford D, Bailey LK, Reed DM, Mitchell JA. Pharmacology and therapeutic potential of pattern recognition receptors. Pharmacol Ther 2012; 135:200-15. [PMID: 22627269 DOI: 10.1016/j.pharmthera.2012.05.007] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2012] [Accepted: 04/20/2012] [Indexed: 12/30/2022]
Abstract
Pharmacologists have used pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS) for decades as a stimulus for studying mediators involved in inflammation and for the screening of anti-inflammatory compounds. However, in the view of immunologists, LPS was too non-specific for studying the mechanisms of immune signalling in infection and inflammation, as no receptors had been identified. This changed in the late 1990s with the discovery of the Toll-like receptors. These 'pattern recognition receptors' (PRRs) were able to recognise highly conserved sequences, the so called pathogen associated molecular patterns (PAMPs) present in or on pathogens. This specificity of particular PAMPs and their newly defined receptors provided a common ground between pharmacologists and immunologists for the study of inflammation. PRRs also recognise endogenous agonists, the so called danger-associated molecular patterns (DAMPs), which can result in sterile inflammation. The signalling pathways and ligands of many PRRs have now been characterised and there is no doubt that this rich vein of research will aid the discovery of new therapeutics for infectious conditions and chronic inflammatory disease.
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Affiliation(s)
- M J Paul-Clark
- Department of Cardiothoracic Pharmacology, Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, Guy Scadding Building, Dovehouse Street, London SW3 6LY, United Kingdom.
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Stefler D, Bhopal R, Fischbacher C. Might infection explain the higher risk of coronary heart disease in South Asians? Systematic review comparing prevalence rates with white populations in developed countries. Public Health 2012; 126:397-409. [DOI: 10.1016/j.puhe.2012.01.033] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2011] [Revised: 12/01/2011] [Accepted: 01/25/2012] [Indexed: 10/28/2022]
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