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Shrestha UM, Chae HD, Fang Q, Lee RJ, Packiasamy J, Huynh L, Blecha J, Huynh TL, VanBrocklin HF, Levi J, Seo Y. A Feasibility Study of [ 18F]F-AraG Positron Emission Tomography (PET) for Cardiac Imaging-Myocardial Viability in Ischemia-Reperfusion Injury Model. Mol Imaging Biol 2024; 26:869-878. [PMID: 39060882 DOI: 10.1007/s11307-024-01932-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 06/05/2024] [Accepted: 07/01/2024] [Indexed: 07/28/2024]
Abstract
PURPOSE Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI. PROCEDURE To test whether the myocardial [18F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [18F]F-AraG uptake in normal heart by comparing [18F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [18F]F-AraG and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [18F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis. RESULTS The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [18F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [18F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [18F]FDG signals showed wider variability at different time points. Noticeable [18F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates. CONCLUSIONS Our preliminary preclinical data show that [18F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.
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Affiliation(s)
- Uttam M Shrestha
- Department of Radiology and Biomedical Imaging, UCSF Physics Research Laboratory, University of California, 185 Berry Street, STE 350, San Francisco, CA, 94143, USA.
| | - Hee-Don Chae
- CellSight Technologies, Inc., 185 Berry Street, STE 350, San Francisco, CA, 94107, USA
| | - Qizhi Fang
- Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, CA, USA
| | - Randall J Lee
- Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, CA, USA
| | - Juliet Packiasamy
- CellSight Technologies, Inc., 185 Berry Street, STE 350, San Francisco, CA, 94107, USA
| | - Lyna Huynh
- CellSight Technologies, Inc., 185 Berry Street, STE 350, San Francisco, CA, 94107, USA
| | - Joseph Blecha
- Department of Radiology and Biomedical Imaging, UCSF Physics Research Laboratory, University of California, 185 Berry Street, STE 350, San Francisco, CA, 94143, USA
| | - Tony L Huynh
- Department of Radiology and Biomedical Imaging, UCSF Physics Research Laboratory, University of California, 185 Berry Street, STE 350, San Francisco, CA, 94143, USA
| | - Henry F VanBrocklin
- Department of Radiology and Biomedical Imaging, UCSF Physics Research Laboratory, University of California, 185 Berry Street, STE 350, San Francisco, CA, 94143, USA
| | - Jelena Levi
- CellSight Technologies, Inc., 185 Berry Street, STE 350, San Francisco, CA, 94107, USA.
| | - Youngho Seo
- Department of Radiology and Biomedical Imaging, UCSF Physics Research Laboratory, University of California, 185 Berry Street, STE 350, San Francisco, CA, 94143, USA
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Kistamás K, Lamberto F, Vaiciuleviciute R, Leal F, Muenthaisong S, Marte L, Subías-Beltrán P, Alaburda A, Arvanitis DN, Zana M, Costa PF, Bernotiene E, Bergaud C, Dinnyés A. The Current State of Realistic Heart Models for Disease Modelling and Cardiotoxicity. Int J Mol Sci 2024; 25:9186. [PMID: 39273136 PMCID: PMC11394806 DOI: 10.3390/ijms25179186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/18/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
One of the many unresolved obstacles in the field of cardiovascular research is an uncompromising in vitro cardiac model. While primary cell sources from animal models offer both advantages and disadvantages, efforts over the past half-century have aimed to reduce their use. Additionally, obtaining a sufficient quantity of human primary cardiomyocytes faces ethical and legal challenges. As the practically unlimited source of human cardiomyocytes from induced pluripotent stem cells (hiPSC-CM) is now mostly resolved, there are great efforts to improve their quality and applicability by overcoming their intrinsic limitations. The greatest bottleneck in the field is the in vitro ageing of hiPSC-CMs to reach a maturity status that closely resembles that of the adult heart, thereby allowing for more appropriate drug developmental procedures as there is a clear correlation between ageing and developing cardiovascular diseases. Here, we review the current state-of-the-art techniques in the most realistic heart models used in disease modelling and toxicity evaluations from hiPSC-CM maturation through heart-on-a-chip platforms and in silico models to the in vitro models of certain cardiovascular diseases.
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Affiliation(s)
- Kornél Kistamás
- BioTalentum Ltd., Aulich Lajos Str 26, H-2100 Gödöllő, Hungary
| | - Federica Lamberto
- BioTalentum Ltd., Aulich Lajos Str 26, H-2100 Gödöllő, Hungary
- Department of Physiology and Animal Health, Institute of Physiology and Animal Nutrition, Hungarian University of Agriculture and Life Sciences, Páter Károly Str 1, H-2100 Gödöllő, Hungary
| | - Raminta Vaiciuleviciute
- Department of Regenerative Medicine, State Research Institute Innovative Medicine Centre, Santariskiu g. 5, LT-08406 Vilnius, Lithuania
| | - Filipa Leal
- Biofabics Lda, Rua Alfredo Allen 455, 4200-135 Porto, Portugal
| | | | - Luis Marte
- Digital Health Unit, Eurecat-Centre Tecnològic de Catalunya, 08005 Barcelona, Spain
| | - Paula Subías-Beltrán
- Digital Health Unit, Eurecat-Centre Tecnològic de Catalunya, 08005 Barcelona, Spain
| | - Aidas Alaburda
- Department of Regenerative Medicine, State Research Institute Innovative Medicine Centre, Santariskiu g. 5, LT-08406 Vilnius, Lithuania
- Institute of Biosciences, Life Sciences Center, Vilnius University, Sauletekio al. 7, LT-10257 Vilnius, Lithuania
| | - Dina N Arvanitis
- Laboratory for Analysis and Architecture of Systems-French National Centre for Scientific Research (LAAS-CNRS), 7 Avenue du Colonel Roche, F-31400 Toulouse, France
| | - Melinda Zana
- BioTalentum Ltd., Aulich Lajos Str 26, H-2100 Gödöllő, Hungary
| | - Pedro F Costa
- Biofabics Lda, Rua Alfredo Allen 455, 4200-135 Porto, Portugal
| | - Eiva Bernotiene
- Department of Regenerative Medicine, State Research Institute Innovative Medicine Centre, Santariskiu g. 5, LT-08406 Vilnius, Lithuania
- Faculty of Fundamental Sciences, Vilnius Tech, Sauletekio al. 11, LT-10223 Vilnius, Lithuania
| | - Christian Bergaud
- Laboratory for Analysis and Architecture of Systems-French National Centre for Scientific Research (LAAS-CNRS), 7 Avenue du Colonel Roche, F-31400 Toulouse, France
| | - András Dinnyés
- BioTalentum Ltd., Aulich Lajos Str 26, H-2100 Gödöllő, Hungary
- Department of Physiology and Animal Health, Institute of Physiology and Animal Nutrition, Hungarian University of Agriculture and Life Sciences, Páter Károly Str 1, H-2100 Gödöllő, Hungary
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Shrestha U, Chae HD, Fang Q, Lee RJ, Packiasamy J, Huynh L, Blecha J, Huynh TL, VanBrocklin HF, Levi J, Seo Y. A feasibility study of [18F]F-AraG positron emission tomography (PET) for cardiac imaging - myocardial viability in ischemia-reperfusion injury model. RESEARCH SQUARE 2024:rs.3.rs-4244476. [PMID: 38746162 PMCID: PMC11092840 DOI: 10.21203/rs.3.rs-4244476/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
Purpose Myocardial infarction (MI) with subsequent inflammation is one of the most common heart conditions leading to progressive tissue damage. A reliable imaging marker to assess tissue viability after MI would help determine the risks and benefits of any intervention. In this study, we investigate whether a new mitochondria-targeted imaging agent, 18F-labeled 2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosylguanine ([18F]F-AraG), a positron emission tomography (PET) agent developed for imaging activated T cells, is suitable for cardiac imaging and to test the myocardial viability after MI. Procedure To test whether the myocardial [18F]-F-AraG signal is coming from cardiomyocytes or immune infiltrates, we compared cardiac signal in wild-type (WT) mice with that of T cell deficient Rag1 knockout (Rag1 KO) mice. We assessed the effect of dietary nucleotides on myocardial [18F]F-AraG uptake in normal heart by comparing [18F]F-AraG signals between mice fed with purified diet and those fed with purified diet supplemented with nucleotides. The myocardial viability was investigated in rodent model by imaging rat with [18F]F-AraG and 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) before and after MI. All PET signals were quantified in terms of the percent injected dose per cc (%ID/cc). We also explored [18F]FDG signal variability and potential T cell infiltration into fibrotic area in the affected myocardium with H&E analysis. Results The difference in %ID/cc for Rag1 KO and WT mice was not significant (p = ns) indicating that the [18F]F-AraG signal in the myocardium was primarily coming from cardiomyocytes. No difference in myocardial uptake was observed between [18F]F-AraG signals in mice fed with purified diet and with purified diet supplemented with nucleotides (p = ns). The [18F]FDG signals showed wider variability at different time points. Noticeable [18F]F-AraG signals were observed in the affected MI regions. There were T cells in the fibrotic area in the H&E analysis, but they did not constitute the predominant infiltrates. Conclusions Our preliminary preclinical data show that [18F]F-AraG accumulates in cardiomyocytes indicating that it may be suitable for cardiac imaging and to evaluate the myocardial viability after MI.
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Affiliation(s)
| | | | | | | | | | - Lyna Huynh
- UCSF: University of California San Francisco
| | | | | | | | - Jelena Levi
- UCSF: University of California San Francisco
| | - Youngho Seo
- UCSF: University of California San Francisco
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Tripathy S, Londhe S, Patra CR. Nitroprusside and metal nitroprusside nano analogues for cancer therapy. Biomed Mater 2024; 19:032001. [PMID: 38387050 DOI: 10.1088/1748-605x/ad2c18] [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: 09/18/2023] [Accepted: 02/22/2024] [Indexed: 02/24/2024]
Abstract
Sodium nitroprusside (SNP), U.S approved drug has been used in clinical emergency as a hypertensive drug for more than a decade. It is well established for its various biomedical applications such as angiogenesis, wound healing, neurological disorders including anti-microbial applications etc. Apart from that, SNP have been considered as excellent biomedical materials for its use as anti-cancer agent because of its behavior as NO-donor. Recent reports suggest that incorporation of metals in SNP/encapsulation of SNP in metal nanoparticles (metal nitroprusside analogues) shows better therapeutic anti-cancer activity. Although there are numerous reports available regarding the biological applications of SNP and metal-based SNP analogue nanoparticles, unfortunately there is not a single comprehensive review which highlights the anti-cancer activity of SNP and its derivative metal analogues in detail along with the future perspective. To this end, the present review article focuses the recent development of anti-cancer activity of SNP and metal-based SNP analogues, their plausible mechanism of action, current status. Furthermore, the future perspectives and challenges of these biomedical materials are also discussed. Overall, this review article represents a new perspective in the area of cancer nanomedicine that will attract a wider spectrum of scientific community.
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Affiliation(s)
- Sanchita Tripathy
- Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, 500007 Telangana, India
- Academy of Scientific and Innovative Research (AcSIR), Gaziabad, 201002 U.P, India
| | - Swapnali Londhe
- Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, 500007 Telangana, India
- Academy of Scientific and Innovative Research (AcSIR), Gaziabad, 201002 U.P, India
| | - Chitta Ranjan Patra
- Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, 500007 Telangana, India
- Academy of Scientific and Innovative Research (AcSIR), Gaziabad, 201002 U.P, India
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de Oliveira Laterza Ribeiro M, Hueb W, Rezende PC, Lima EG, Nomura CH, Rochitte CE, da Silva Selistre L, Boros GAB, Ramires JAF, Filho RK. Myocardial tissue microstructure with and without stress-induced ischemia assessed by T1 mapping in patients with stable coronary artery disease. Clin Imaging 2023; 101:142-149. [PMID: 37348160 DOI: 10.1016/j.clinimag.2023.06.004] [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: 02/06/2023] [Revised: 04/28/2023] [Accepted: 06/05/2023] [Indexed: 06/24/2023]
Abstract
BACKGROUND Stress-induced myocardial ischemia seems not to be associated with cardiovascular events. However, its effects on myocardial tissue characteristics remain under debate. Thus, we sought to assess whether documented stress-induced ischemia is associated with changes in myocardial microstructure evaluated by magnetic resonance native T1 map and extracellular volume fraction (ECV). METHODS This is a single-center, analysis of the previously published MASS V Trial. Multivessel patients with a formal indication for myocardial revascularization and with documented stress-induced ischemia were included in this study. Native T1 and ECV values evaluated by cardiac magnetic resonance imaging of ischemic and nonischemic myocardial segments at rest and after stress were compared. Myocardial ischemia was detected by either nuclear scintigraphy or stress magnetic cardiac resonance protocol. RESULTS Between May 2012 and March 2014, 326 prospective patients were eligible for isolated CABG or PCI and 219 were included in the MASS V trial. All patients underwent resting cardiac magnetic resonance imaging. Of a total of 840 myocardial segments, 654 were nonischemic segments and 186 were ischemic segments. Native T1 and ECV values of ischemic segments were not significantly different from nonischemic segments, both at rest and after stress induction. In addition, native T1 and ECV values of myocardial segments supplied by vessels with obstructive lesions were similar to those supplied by nonobstructive ones. CONCLUSION AND RELEVANCE In this study, cardiac magnetic resonance identified similar T1 mapping values between ischemic and nonischemic myocardial segments. This finding suggests integrity and stability of myocardial tissue in the presence of stress-induced ischemia.
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Affiliation(s)
| | - Whady Hueb
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil.
| | - Paulo Cury Rezende
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Eduardo Gomes Lima
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Cesar Higa Nomura
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Carlos Eduardo Rochitte
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | | | - Gustavo André Boeing Boros
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Jose Antonio Franchini Ramires
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
| | - Roberto Kalil Filho
- Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, SP, Brazil
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Sabe SA, Harris DD, Broadwin M, Sabra M, Xu CM, Banerjee D, Abid MR, Sellke FW. Sitagliptin therapy improves myocardial perfusion and arteriolar collateralization in chronically ischemic myocardium: A pilot study. Physiol Rep 2023; 11:e15744. [PMID: 37300400 PMCID: PMC10257079 DOI: 10.14814/phy2.15744] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/15/2023] [Accepted: 05/15/2023] [Indexed: 06/12/2023] Open
Abstract
Dipeptidyl peptidase 4 inhibitors (DPP4i) may be cardioprotective based on several small animal and clinical studies, though randomized control trials have demonstrated limited benefit. Given these discrepant findings, the role of these agents in chronic myocardial disease, particularly in the absence of diabetes, is still poorly understood. The purpose of this study was to determine the effects of sitagliptin, a DPP4i, on myocardial perfusion and microvessel density in a clinically relevant large animal model of chronic myocardial ischemia. Normoglycemic Yorkshire swine underwent ameroid constrictor placement to the left circumflex artery to induce chronic myocardial ischemia. Two weeks later, pigs received either no drug (CON, n = 8) or 100 mg oral sitagliptin (SIT) daily (n = 5). Treatment continued for 5 weeks, followed by hemodynamic measurements, euthanasia, and tissue harvest of ischemic myocardium. There were no significant differences in myocardial function between CON and SIT as measured by stroke work (p > 0.5), cardiac output (p = 0.22), and end-systolic elastance (p = 0.17). SIT was associated with increased absolute blood flow at rest (17% increase, IQR 12-62, p = 0.045) and during pacing (89% increase, IQR 83-105, p = 0.002). SIT was also associated with improved arteriolar density (p = 0.045) compared with CON, without changes in capillary density (p = 0.72). SIT was associated with increased expression of pro-arteriogenic markers MCP-1 (p = 0.003), TGFß (p = 0.03), FGFR1 (p = 0.002), and ICAM-1 (p = 0.03), with a trend toward an increase in the ratio of phosphorylated/active PLCγ1 to total PLCγ1 (p = 0.11) compared with CON. In conclusion, in chronically ischemic myocardium, sitagliptin improves myocardial perfusion and arteriolar collateralization via the activation of pro-arteriogenic signaling pathways.
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Affiliation(s)
- Sharif A. Sabe
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island HospitalAlpert Medical School of Brown University, Rhode Island HospitalProvidenceRhode IslandUSA
| | - Dwight Douglas Harris
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island HospitalAlpert Medical School of Brown University, Rhode Island HospitalProvidenceRhode IslandUSA
| | - Mark Broadwin
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island HospitalAlpert Medical School of Brown University, Rhode Island HospitalProvidenceRhode IslandUSA
| | - Mohamed Sabra
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island HospitalAlpert Medical School of Brown University, Rhode Island HospitalProvidenceRhode IslandUSA
| | - Cynthia M. Xu
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island HospitalAlpert Medical School of Brown University, Rhode Island HospitalProvidenceRhode IslandUSA
| | - Debolina Banerjee
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island HospitalAlpert Medical School of Brown University, Rhode Island HospitalProvidenceRhode IslandUSA
| | - M. Ruhul Abid
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island HospitalAlpert Medical School of Brown University, Rhode Island HospitalProvidenceRhode IslandUSA
| | - Frank W. Sellke
- Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island HospitalAlpert Medical School of Brown University, Rhode Island HospitalProvidenceRhode IslandUSA
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Ahmad T, Khan T, Kirabo A, Shah AJ. Antioxidant Flavonoid Diosmetin Is Cardioprotective in a Rat Model of Myocardial Infarction Induced by Beta 1-Adrenergic Receptors Activation. Curr Issues Mol Biol 2023; 45:4675-4686. [PMID: 37367046 PMCID: PMC10297416 DOI: 10.3390/cimb45060297] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 05/23/2023] [Accepted: 05/24/2023] [Indexed: 06/28/2023] Open
Abstract
Myocardial infarction (MI) is a common and life-threatening manifestation of ischemic heart diseases (IHD). The most important risk factor for MI is hypertension. Natural products from medicinal plants have gained considerable attention globally due to their preventive and therapeutic effects. Flavonoids have been found to be efficacious in ischemic heart diseases (IHD) by alleviating oxidative stress and beta-1 adrenergic activation, but the mechanistic link is not clear. We hypothesized that antioxidant flavonoid diosmetin is cardioprotective in a rat model of MI induced by beta 1-adrenergic receptor activation. To test this hypothesis, we evaluated the cardioprotective potential of diosmetin on isoproterenol-induced MI in rats by performing lead II electrocardiography (ECG), cardiac biomarkers including troponin I (cTnI) and creatinine phosphokinase (CPK), CK-myocardial band, (CK-MB), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotranferase (AST) by using biolyzer 100, as well as histopathological analysis. We found that diosmetin (1 and 3 mg/kg) attenuated isoproterenol-induced elevation in the T-wave and deep Q-wave on the ECG, as well as heart-to-body weight ratio and infarction size. In addition, pretreatment with diosmetin attenuated the isoproterenol-induced increase in serum troponin I. These results demonstrate that flavonoid diosmetin may provide therapeutic benefit in myocardial infarction.
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Affiliation(s)
- Taseer Ahmad
- Department of Pharmacy, Abbottabad Campus, COMSATS University Islamabad, University Road, Abbottabad 22060, Pakistan
- Laboratory of Cardiovascular Research and Integrative Pharmacology, College of Pharmacy, University of Sargodha, University Road, Sargodha 40100, Pakistan
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Taous Khan
- Laboratory of Cardiovascular Research and Integrative Pharmacology, College of Pharmacy, University of Sargodha, University Road, Sargodha 40100, Pakistan
| | - Annet Kirabo
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Abdul Jabbar Shah
- Laboratory of Cardiovascular Research and Integrative Pharmacology, College of Pharmacy, University of Sargodha, University Road, Sargodha 40100, Pakistan
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Duca ȘT, Roca M, Costache AD, Chetran A, Afrăsânie I, Miftode RȘ, Tudorancea I, Matei I, Ciorap RG, Mitu O, Bădescu MC, Iliescu-Halitchi D, Halițchi-Iliescu CO, Mitu F, Lionte C, Costache II. T-Wave Analysis on the 24 h Holter ECG Monitoring as a Predictive Assessment of Major Adverse Cardiovascular Events in Patients with Myocardial Infarction: A Literature Review and Future Perspectives. Life (Basel) 2023; 13:life13051155. [PMID: 37240799 DOI: 10.3390/life13051155] [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: 03/05/2023] [Revised: 05/01/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Myocardial ischemia is a pathophysiological state characterized by inadequate perfusion of the myocardium, resulting in an imbalance between myocardial oxygen demand and supply. It is most commonly caused by coronary artery disease, in which atherosclerotic plaques lead to luminal narrowing and reduced blood flow to the heart. Myocardial ischemia can manifest as angina pectoris or silent myocardial ischemia and can progress to myocardial infarction or heart failure if left untreated. Diagnosis of myocardial ischemia typically involves a combination of clinical evaluation, electrocardiography and imaging studies. Electrocardiographic parameters, as assessed by 24 h Holter ECG monitoring, can predict the occurrence of major adverse cardiovascular events in patients with myocardial ischemia, independent of other risk factors. The T-waves in patients with myocardial ischemia have prognostic value for predicting major adverse cardiovascular events, and their electrophysiological heterogeneity can be visualized using various techniques. Combining the electrocardiographic findings with the assessment of myocardial substrate may offer a better picture of the factors that can contribute to cardiovascular death.
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Affiliation(s)
- Ștefania-Teodora Duca
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Mihai Roca
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiovascular Rehabilitation, Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Alexandru-Dan Costache
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiovascular Rehabilitation, Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Adriana Chetran
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Irina Afrăsânie
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Radu-Ștefan Miftode
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Ionuț Tudorancea
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
- Department of Morpho-Functional Science II-Physiology, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
| | - Iulian Matei
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Radu-George Ciorap
- Department of Biomedical Science, Faculty of Medical Bioengineering, University of Medicine and Pharmacy "Grigore T. Popa", 700145 Iasi, Romania
| | - Ovidiu Mitu
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Minerva Codruța Bădescu
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of III Internal Medicine Clinic, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
| | - Dan Iliescu-Halitchi
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, Arcadia Hospital, 700620 Iasi, Romania
| | - Codruța-Olimpiada Halițchi-Iliescu
- Department of Mother and Child Medicine-Pediatrics, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Pedriatics, Arcadia Hospital, 700620 Iasi, Romania
| | - Florin Mitu
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiovascular Rehabilitation, Clinical Rehabilitation Hospital, 700661 Iasi, Romania
| | - Cătălina Lionte
- Department of Internal Medicine III, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700145 Iasi, Romania
- Department of Cardiology, Helicomed Hospital, 700115 Iasi, Romania
| | - Irina-Iuliana Costache
- Department of Internal Medicine I, Faculty of Medicine, University of Medicine and Pharmacy "Grigore T. Popa", 700115 Iasi, Romania
- Department of Cardiology, "St. Spiridon" Emergency County Hospital, 700111 Iasi, Romania
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Liu L, Hu J, Mao Q, Liu C, He H, Hui X, Yang G, Qu P, Lian W, Duan L, Dong Y, Pan J, Liu Y, He Q, Li J, Wang J. Functional compounds of ginseng and ginseng-containing medicine for treating cardiovascular diseases. Front Pharmacol 2022; 13:1034870. [PMID: 36532771 PMCID: PMC9755186 DOI: 10.3389/fphar.2022.1034870] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 11/24/2022] [Indexed: 10/29/2023] Open
Abstract
Ginseng (Panax ginseng C.A.Mey.) is the dry root and rhizome of the Araliaceae ginseng plant. It has always been used as a tonic in China for strengthening the body. Cardiovascular disease is still the main cause of death in the world. Some studies have shown that the functional components of ginseng can regulate the pathological process of various cardiovascular diseases through different mechanisms, and its formulation also plays an irreplaceable role in the clinical treatment of cardiovascular diseases. Therefore, this paper elaborates the current pharmacological effects of ginseng functional components in treating cardiovascular diseases, summarizes the adverse reactions of ginseng, and sorts out the Chinese patent medicines containing ginseng formula which can treat cardiovascular diseases.
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Affiliation(s)
- Lanchun Liu
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jun Hu
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qiyuan Mao
- Departmen of Oncology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chao Liu
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Haoqiang He
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaoshan Hui
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Guang Yang
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Peirong Qu
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wenjing Lian
- Beijing University of Chinese Medicine, Beijing, China
| | - Lian Duan
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yan Dong
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Juhua Pan
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yongmei Liu
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qingyong He
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jun Li
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jie Wang
- Departmen of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Ahmad T, Khan T, Tabassum T, Alqahtani YS, Mahnashi MH, Alyami BA, Alqarni AO, Alasmary MY, Almedhesh SA, Shah AJ. Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats. Curr Issues Mol Biol 2022; 44:3180-3193. [PMID: 35877444 PMCID: PMC9319353 DOI: 10.3390/cimb44070220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/13/2022] [Accepted: 07/13/2022] [Indexed: 11/22/2022] Open
Abstract
Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent.
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Affiliation(s)
- Taseer Ahmad
- Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, University Road, Abbottabad 22060, Pakistan; (T.A.); (T.K.)
- Laboratory of Cardiovascular Research and Integrative Pharmacology, College of Pharmacy, University of Sargodha, Sargodha 40100, Pakistan
| | - Taous Khan
- Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, University Road, Abbottabad 22060, Pakistan; (T.A.); (T.K.)
| | - Tahira Tabassum
- Department Pathology, Sargodha Medical College, University of Sargodha, Sargodha 40100, Pakistan;
| | - Yahya S. Alqahtani
- Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran 61441, Saudi Arabia; (Y.S.A.); (M.H.M.); (B.A.A.); (A.O.A.)
| | - Mater H. Mahnashi
- Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran 61441, Saudi Arabia; (Y.S.A.); (M.H.M.); (B.A.A.); (A.O.A.)
| | - Bandar A. Alyami
- Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran 61441, Saudi Arabia; (Y.S.A.); (M.H.M.); (B.A.A.); (A.O.A.)
| | - Ali O. Alqarni
- Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran 61441, Saudi Arabia; (Y.S.A.); (M.H.M.); (B.A.A.); (A.O.A.)
| | - Mohammed Y. Alasmary
- Medical Department, College of Medicine, Najran University, Najran 61441, Saudi Arabia;
| | - Sultan A. Almedhesh
- Pediatric Department, College of Medicine, Najran University, Najran 61441, Saudi Arabia;
| | - Abdul Jabbar Shah
- Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, University Road, Abbottabad 22060, Pakistan; (T.A.); (T.K.)
- Correspondence:
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Akbar MR, Adiputro DL, Tiksnadi BB, Soeriadi EA, Hasan M, Muttaqien F, Raharjo PP, Nurazizah E, Tarsidin NF. Case Series: Extracorporeal Shockwave Myocardial Revascularization Therapy Improves Ischemic Response, Functional Capacity, and Quality of Life in Indicated CABG-Stable Angina Pectoris Patients. Front Cardiovasc Med 2022; 9:799834. [PMID: 35224043 PMCID: PMC8874125 DOI: 10.3389/fcvm.2022.799834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 01/11/2022] [Indexed: 11/13/2022] Open
Abstract
IntroductionExtracorporeal shockwave myocardial revascularization (ESMR) is included in the guidelines only for patients with refractory angina pectoris having no option for invasive revascularization. We intend to report a case series with ESMR therapy is indicated patients with coronary artery bypass grafting-stable angina pectoris (CABG-SAP) who refuse the surgery, irrespective of angina symptoms.MethodsWe review medical records of patients with SAP admitted to ESMR therapy in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia from January 2018 to December 2019. Recorded variables at baseline and after therapy extracted, namely, (1) ischemic response, double product, and (2) functional capacity measured as metabolic equivalent (MET) using treadmill test; (3) six-minute walking test distance achieved; and (4) quality of life using SF-36 Questionnaire.ResultsA total of four indicated patients with CABG-SAP from 50 to 75 years old were included in this study. At baseline, one patient is CCS class I and two patients are CCS class II with SDS ranging from 3 to 17. Ischemic response improved in all the patients. The double product improved in patient 1 9,600–14,872 mm Hg × bpm, patient 2 9,460–10,640 mm Hg × bpm, and patient 4 17,220–20,480 mm Hg × bpm. The functional capacity improved in Patient 1 8.07–8.91 METs, patient 2 1.91–4.01 METs, patient 3 3.45–6.39 METs, and patient 4 3.9–4.43 METs. The 6-min walking distance improved in patient 1 540–570 m and patient 2 345–405 m. The CCS class, bodily pain, and general health domain scores improved in all patients.ConclusionESMR therapy might be beneficial for indicated patients with CABG-SAP to improve ischemic response, functional capacity, and physical component of quality of life.
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Affiliation(s)
- Mohammad Rizki Akbar
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Dr. Hasan Sadikin General Hospital, Padjadjaran University, Bandung, Indonesia
- *Correspondence: Mohammad Rizki Akbar
| | - Dwi Laksono Adiputro
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Ulin General Hospital, Lambung Mangkurat University, Banjarmasin, Indonesia
| | - Badai Bhatara Tiksnadi
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Dr. Hasan Sadikin General Hospital, Padjadjaran University, Bandung, Indonesia
| | - Erwin Affandi Soeriadi
- Department of Nuclear Medicine and Molecular Imaging, Faculty of Medicine, Dr. Hasan Sadikin General Hospital, Padjadjaran University, Bandung, Indonesia
| | - Melawati Hasan
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Dr. Hasan Sadikin General Hospital, Padjadjaran University, Bandung, Indonesia
| | - Fauzan Muttaqien
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Ulin General Hospital, Lambung Mangkurat University, Banjarmasin, Indonesia
| | - Pradana Pratomo Raharjo
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Dr. Hasan Sadikin General Hospital, Padjadjaran University, Bandung, Indonesia
| | - Eliza Nurazizah
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Dr. Hasan Sadikin General Hospital, Padjadjaran University, Bandung, Indonesia
| | - Najmi Fauzan Tarsidin
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Dr. Hasan Sadikin General Hospital, Padjadjaran University, Bandung, Indonesia
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Hospitalization Expenses and Influencing Factors for Inpatients with Ischemic Heart Disease in Iran: A Retrospective Study. HEALTH SCOPE 2022. [DOI: 10.5812/jhealthscope.117711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Ischemic heart disease (IHD) is the leading cause of death and disability worldwide and in Iran, which imposes a heavy financial burden both on patient’s family and society. Objectives: This study aimed to analyze the direct medical costs of inpatients with IHD and its influencing factors in Iran in 2020. Methods: The sample of this cross-sectional study included 41,357 patients with IHD selected from the hospital information system (HIS) of the Iran Health Insurance Organization from August 23, 2019, to June 20, 2020. The study used the claims data of these patients, which included their demographics, length of stay (LOS), intensive care unit (ICU) admission, hospital accreditation grade, hospital ownership type, and patient discharge status. The multiple linear regression model was employed to evaluate the relationship between hospitalization costs and the associated factors. All statistical tests were conducted at the significance level of P < 0.05 using the R 3.6.3 software. Results: The mean age of patients was 63.95 ± 12.63 years old, and most of them were male (54.4%). The mean hospitalization cost per patient and per day was 586.42 ± 472.51 USD and 103.64 ± 100.29 USD, respectively. Moreover, the mean LOS was 4.92 days. Drugs and consumable medical supplies, as well as nursing and hoteling services, had the highest shares of hospitalization costs (29.54% and 29.4%, respectively). The hospitalization costs of patients with IHD were higher among men (β = 1.24), age 61 - 70 years (β = 1.38), LOS ≥ 5 (β = 2.92), ICU admission (β = 1.62), Iranian health fund (β = 1.21), and private hospitals (β = 1.91). Top-grade and first-grade hospitals had higher costs compared to grade 2 (β = 0.67), grade 3 (β = 0.35), and grade 4 (β = 0.72) hospitals. Deceased patients had also higher costs than patients with complete recovery (β = 0.63), relative recovery (β = 0.59), follow-up (β = 0.51), transfer to other medical centers (β = 0.44), and discharge against medical advice (DAMA) (β = 0.62). Conclusions: According to the results, shortening the LOS and controlling the high costs of drugs and consumable medical supplies are among the main strategies to reduce high hospitalization costs.
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Impaired tricarboxylic acid cycle flux and mitochondrial aerobic respiration during isoproterenol induced myocardial ischemia is rescued by bilobalide. J Pharm Anal 2022; 11:764-775. [PMID: 35028182 PMCID: PMC8740385 DOI: 10.1016/j.jpha.2020.08.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 08/12/2020] [Accepted: 08/13/2020] [Indexed: 11/24/2022] Open
Abstract
There is an urgent need to elucidate the pathogenesis of myocardial ischemia (MI) and potential drug treatments. Here, the anti-MI mechanism and material basis of Ginkgo biloba L. extract (GBE) were studied from the perspective of energy metabolism flux regulation. Metabolic flux analysis (MFA) was performed to investigate energy metabolism flux disorder and the regulatory nodes of GBE components in isoproterenol (ISO)-induced ischemia-like cardiomyocytes. It showed that [U–13C] glucose derived m+2 isotopologues from the upstream tricarboxylic acid (TCA) cycle metabolites were markedly accumulated in ISO-injured cardiomyocytes, but the opposite was seen for the downstream metabolites, while their total cellular concentrations were increased. This indicates a blockage of carbon flow from glycolysis and enhanced anaplerosis from other carbon sources. A Seahorse test was used to screen for GBE components with regulatory effects on mitochondrial aerobic respiratory dysfunction. It showed that bilobalide protected against impaired mitochondrial aerobic respiration. MFA also showed that bilobalide significantly modulated the TCA cycle flux, reduced abnormal metabolite accumulation, and balanced the demand of different carbon sources. Western blotting and PCR analysis showed that bilobalide decreased the enhanced expression of key metabolic enzymes in injured cells. Bilobalide's efficacy was verified by in vivo experiments in rats. This is the first report to show that bilobalide, the active ingredient of GBE, protects against MI by rescuing impaired TCA cycle flux. This provides a new mechanism and potential drug treatment for MI. It also shows the potential of MFA/Seahorse combination as a powerful strategy for pharmacological research on herbal medicine.
A strategy for herbal medicine research by stable isotopic tracing metabolic flux analysis combined with Seahorse test. A blockage of carbon flow from glycolysis and enhanced anaplerosis in TCA cycle during myocardial ischemia. Bilobalide is against myocardial ischemia by rescuing impaired TCA cycle flux and mitochondrial aerobic respiration.
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Protection of CAPE-pNO 2 Against Chronic Myocardial Ischemia by the TGF-Β1/Galectin-3 Pathway In Vivo and In Vitro. Inflammation 2021; 45:1039-1058. [PMID: 34817763 DOI: 10.1007/s10753-021-01600-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 11/05/2021] [Accepted: 11/09/2021] [Indexed: 10/19/2022]
Abstract
Although it is known that caffeic acid phenethyl ester (CAPE) and its derivatives could ameliorate acute myocardial injury, their effects on chronic myocardial ischemia (CMI) were not reported. This study aimed to investigate the potential effect of caffeic acid p-nitro phenethyl ester (CAPE-pNO2, a derivative of CAPE) on CMI and underlying mechanisms. SD rats were subjected to high-fat-cholesterol-diet (HFCD) and vitamin D3, and the H9c2 cells were treated with LPS to establish CMI model, followed by the respective treatment with saline, CAPE, or CAPE-pNO2. In vivo, CAPE-pNO2 could reduce serum lipid levels and improve impaired cardiac function and morphological changes. Data of related assays indicated that CAPE-pNO2 downregulated the expression of transforming growth factor-β1 (TGF-β1) and galectin-3 (Gal-3). Besides, CAPE-pNO2 decreased collagen deposition, the number of apoptotic cardiomyocytes, and some related downstream proteins of Gal-3 in the CMI rats. Interestingly, the effects of CAPE-pNO2 on TGF-β1, Gal-3, and other proteins expressed in the lung were consistent with that in the heart. In vitro, CAPE-pNO2 could attenuate the fibrosis, apoptosis, and inflammation by activating TGF-β1/Gal-3 pathway in LPS-induced H9c2 cell. However, CAPE-pNO2-mediated cardioprotection can be eliminated when treated with modified citrus pectin (MCP, an inhibitor of Gal-3). And in comparison, CAPE-pNO2 presented stronger effects than CAPE. This study indicates that CAPE-pNO2 may ameliorate CMI by suppressing fibrosis, inflammation, and apoptosis via the TGF-β1/Gal-3 pathway in vivo and in vitro.
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15
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Gebremedhin MH, Gebrekirstos LG. Dietary and Behavioral Risk Factors of Ischemic Heart Disease Among Patients of Medical Outpatient Departments in Southern Ethiopia: Unmatched Case-Control Study. Integr Blood Press Control 2021; 14:123-132. [PMID: 34588813 PMCID: PMC8473848 DOI: 10.2147/ibpc.s322663] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 09/08/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Worldwide mortality due to cardiovascular disease is the dominant cause of death, and ischemic heart disease is the leading one. Though risk factors for Ischemic heart diseases are modifiable and preventable, it is not well investigated in the local context. Thus, this study aimed to assess the dietary and behavioral risk factors for ischemic heart disease among patients in medical outpatient departments in Southern, Ethiopia. METHODS A facility-based unmatched case-control study was conducted from November 16 to March 20, 2020, among patients with ischemic heart disease and those patients who visited the three hospitals of the Wolaita Zone. A convenient sampling method was used and the data were entered using Epi data version 3.1 and exported to SPSS version 21 for analysis, a p-value <0.05, were considered statistically significant. RESULTS A total of 557 study participants (140 cases and 417 controls) were included in a ratio of 1:3. The adjusted odds ratio for having no formal education (AOR = 3.18; 95% CI: 1.59, 6.34), previous history of hypertension (AOR= 2.84; 95% CI: 1.73, 4.66), physical inactivity (AOR= 2.23; 95% CI: 1.32, 3.76), inadequate intake of fruit and vegetable consumption (AOR= 2.43; 95% CI; 1.40, 4,22), palm oil use for food preparation (AOR= 2.12; 95% CI: 1.23, 3.63) and obesity (AOR= 5.68; 95% CI: 2.63, 12.23) increased the occurrence of the disease. CONCLUSION Although ischemic heart disease is preventable, using relatively simple and inexpensive lifestyle changes, it is projected to cause preventable loss of life. So, expanding health education and healthy life styles including exercise is recommended.
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Affiliation(s)
- Meron Hadis Gebremedhin
- School of medicine, College of health science and medicine, Wolaita Sodo University, Wolaita Sodo, Ethiopia
| | - Lielt Gebreselassie Gebrekirstos
- Department of maternity and reproductive health, College of health science and medicine, Wolaita Sodo University, Wolaita Sodo, Ethiopia
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Yin Q, Wang P, Wu X. MicroRNA -148 alleviates cardiac dysfunction, immune disorders and myocardial apoptosis in myocardial ischemia-reperfusion (MI/R) injury by targeting pyruvate dehydrogenase kinase (PDK4). Bioengineered 2021; 12:5552-5565. [PMID: 34517782 PMCID: PMC8806724 DOI: 10.1080/21655979.2021.1965812] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Ischemic heart disease in children may be induced by varied factors, and there is no corresponding systematic treatment up to now. This study aims to investigate the effects of microRNA (miR)-148 on myocardial injury in immature rats with myocardial ischemia-reperfusion (MI/R) injury. In this study, MI/R model was established by ligating the coronary artery of heart. The results showed that miR-148 alleviated myocardial injury and rescued relevant parameters (mean ventricular systolic blood pressure (MAP), left ventricular systolic blood pressure (LVSP), heart rate (HR), creatine kinase-MB (CK-MB), cTn1 and Mb in immature rats with MI/R injury. Besides, miR-148 improved the immune dysfunction induced by MI/R through increasing the number of interleukin (IL)-10+ cells and reducing the number of inducible nitric oxide synthase (iNOS)+ cells. In addition, miR-148 relieved the apoptosis of cardiomyocytes induced by MI/R through inhibiting the expression of Bax and elevating the expression of Bcl-2. Further molecular mechanism indicated that pyruvate dehydrogenase kinase 4 (PDK4) was the downstream target of miR-148, which was further confirmed by dual luciferase reporter assay and related expression detection. Accordingly, silenced PDK4 attenuated cardiac dysfunction, immune disorder and myocardial apoptosis in immature rats and enhanced the ability of antioxidant enzymes. What is more, activated SMAD pathway induced by MI/R injury was then blocked by silenced PDK4. Taken together, our study demonstrated that overexpressed miR-148 relieved cardiac dysfunction, immune disorder and cardiomyocyte apoptosis in immature MI/R rats by PDK4 inhibition, which provided novel targets for MI/R injury treatment.
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Affiliation(s)
- Qi Yin
- Department of Health care center, Hainan People's Hospital, Haikou, Hainan, China
| | - Ping Wang
- Department of Health care center, Hainan People's Hospital, Haikou, Hainan, China
| | - Xiaohua Wu
- Department of Health care center, Hainan People's Hospital, Haikou, Hainan, China
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Rumanti AP, Maruf A, Liu H, Ge S, Lei D, Wang G. Engineered bioresponsive nanotherapeutics: recent advances in the treatment of atherosclerosis and ischemic-related disease. J Mater Chem B 2021; 9:4804-4825. [PMID: 34085084 DOI: 10.1039/d1tb00330e] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Biological stimuli that are present during the pathogenesis of disease have gained considerable interest as a critical element for the design of smart drug delivery systems. Recently, the utilization of biological stimuli-responsive (bioresponsive) nanotheranostic agents to treat atherosclerosis and ischemic-related diseases has demonstrated significant outcomes in preclinical studies. Those diseases share similar hallmarks, including high levels of endogenous reactive oxygen species (ROS), low pH, and high enzyme activity. Interestingly, other relevant biological stimuli such as shear stress, cholesterol, and glutathione have recently been explored as internal stimuli to trigger drug release and some particular actions. In addition, a number of strategies can be proposed to enhance their targeting efficiency, diagnostic properties, and efficacy rate. This review discusses recent advancements in the preclinical studies of bioresponsive nanotherapeutics as diagnostic and therapeutic agents against atherosclerosis and ischemic-related diseases as well as some potential strategies to overcome the current limitations.
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Affiliation(s)
- Ayu Pratiwi Rumanti
- Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College, Faculty of Medicine, Chongqing University, Chongqing, 400030, China.
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Matta A, Nader V, Galinier M, Roncalli J. Transplantation of CD34+ cells for myocardial ischemia. World J Transplant 2021; 11:138-146. [PMID: 34046316 PMCID: PMC8131931 DOI: 10.5500/wjt.v11.i5.138] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/01/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
CD34+ cells are multipotent hematopoietic stem cells also known as endothelial progenitor cells and are useful in regenerative medicine. Naturally, these cells are mobilized from the bone marrow into peripheral circulation in response to ischemic tissue injury. CD34+ cells are known for their high proliferative and differentiation capacities that play a crucial role in the repair process of myocardial damage. They have an important paracrine activity in secreting factors to stimulate vasculogenesis, reduce endothelial cells and cardiomyocytes apoptosis, remodel extracellular matrix and activate additional progenitor cells. Once they migrate to the target site, they enhance angiogenesis, neovascularization and tissue regeneration. Several trials have demonstrated the safety and efficacy of CD34+ cell therapy in different settings, such as peripheral limb ischemia, stroke and cardiovascular disease. Herein, we review the potential utility of CD34+ cell transplantation in acute myocardial infarction, refractory angina and ischemic heart failure.
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Affiliation(s)
- Anthony Matta
- Department of Cardiology, Institute CARDIOMET, University Hospital of Toulouse, Toulouse 31059, France
- Faculty of Medicine, Holy Spirit University of Kaslik, Kaslik 00000, Lebanon
| | - Vanessa Nader
- Department of Cardiology, Institute CARDIOMET, University Hospital of Toulouse, Toulouse 31059, France
- Faculty of Pharmacy, Lebanese University, Beirut 961, Lebanon
| | - Michel Galinier
- Department of Cardiology, Institute CARDIOMET, University Hospital of Toulouse, Toulouse 31059, France
| | - Jerome Roncalli
- Department of Cardiology, Institute CARDIOMET, University Hospital of Toulouse, Toulouse 31059, France
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Pasqua T, Rocca C, Giglio A, Angelone T. Cardiometabolism as an Interlocking Puzzle between the Healthy and Diseased Heart: New Frontiers in Therapeutic Applications. J Clin Med 2021; 10:721. [PMID: 33673114 PMCID: PMC7918460 DOI: 10.3390/jcm10040721] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 02/05/2021] [Accepted: 02/07/2021] [Indexed: 12/14/2022] Open
Abstract
Cardiac metabolism represents a crucial and essential connecting bridge between the healthy and diseased heart. The cardiac muscle, which may be considered an omnivore organ with regard to the energy substrate utilization, under physiological conditions mainly draws energy by fatty acids oxidation. Within cardiomyocytes and their mitochondria, through well-concerted enzymatic reactions, substrates converge on the production of ATP, the basic chemical energy that cardiac muscle converts into mechanical energy, i.e., contraction. When a perturbation of homeostasis occurs, such as an ischemic event, the heart is forced to switch its fatty acid-based metabolism to the carbohydrate utilization as a protective mechanism that allows the maintenance of its key role within the whole organism. Consequently, the flexibility of the cardiac metabolic networks deeply influences the ability of the heart to respond, by adapting to pathophysiological changes. The aim of the present review is to summarize the main metabolic changes detectable in the heart under acute and chronic cardiac pathologies, analyzing possible therapeutic targets to be used. On this basis, cardiometabolism can be described as a crucial mechanism in keeping the physiological structure and function of the heart; furthermore, it can be considered a promising goal for future pharmacological agents able to appropriately modulate the rate-limiting steps of heart metabolic pathways.
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Affiliation(s)
- Teresa Pasqua
- Department of Health Science, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy;
| | - Carmine Rocca
- Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, E. and E.S. (Di.B.E.S.T.), University of Calabria, 87036 Rende (CS), Italy
| | - Anita Giglio
- Department of Biology, E. and E.S. (Di.B.E.S.T.), University of Calabria, 87036 Rende (CS), Italy;
| | - Tommaso Angelone
- Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, E. and E.S. (Di.B.E.S.T.), University of Calabria, 87036 Rende (CS), Italy
- National Institute of Cardiovascular Research (I.N.R.C.), 40126 Bologna, Italy
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20
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Sarhene M, Ni JY, Duncan ES, Liu Z, Li S, Zhang J, Guo R, Gao S, Gao X, Fan G. Ginsenosides for cardiovascular diseases; update on pre-clinical and clinical evidence, pharmacological effects and the mechanisms of action. Pharmacol Res 2021; 166:105481. [PMID: 33549726 DOI: 10.1016/j.phrs.2021.105481] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 01/20/2021] [Accepted: 02/02/2021] [Indexed: 12/14/2022]
Abstract
Cardiovascular disease (CVD) remains the major cause of death worldwide, accounting for almost 31% of the global mortality annually. Several preclinical studies have indicated that ginseng and the major bioactive ingredient (ginsenosides) can modulate several CVDs through diverse mechanisms. However, there is paucity in the translation of such experiments into clinical arena for cardiovascular ailments due to lack of conclusive specific pathways through which these activities are initiated and lack of larger, long-term well-structured clinical trials. Therefore, this review elaborates on current pharmacological effects of ginseng and ginsenosides in the cardiovascular system and provides some insights into the safety, toxicity, and synergistic effects in human trials. The review concludes that before ginseng, ginsenosides and their preparations could be utilized in the clinical treatment of CVDs, there should be more preclinical studies in larger animals (like the guinea pig, rabbit, dog, and monkey) to find the specific dosages, address the toxicity, safety and synergistic effects with other conventional drugs. This could lead to the initiation of large-scale, long-term well-structured randomized, and placebo-controlled clinical trials to test whether treatment is effective for a longer period and test the efficacy against other conventional therapies.
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Affiliation(s)
- Michael Sarhene
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Jing Yu Ni
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Esi Sophia Duncan
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Zhihao Liu
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Sheng Li
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Jing Zhang
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Rui Guo
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Shan Gao
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiumei Gao
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Guanwei Fan
- First teaching hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China.
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21
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Soluble CD40 ligand expression in stable atherosclerosis: A systematic review and meta-analysis. Atherosclerosis 2020; 319:86-100. [PMID: 33494009 DOI: 10.1016/j.atherosclerosis.2020.12.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 11/08/2020] [Accepted: 12/11/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIMS The role of inflammation in atherosclerosis development and expression in different arterial territories is unclear. Soluble CD40 ligand (sCD40L) mediates inflammation and atherogenesis. Through a systematic review and meta-analysis, we assessed whether sCD40L was dysregulated in stable atherosclerosis, irrespective of the diseased arterial territory, and whether this dysregulation differed according to the specific territory. METHODS Systematic literature searches were performed in MEDLINE, Cochrane Library, Web of Science, and Embase for studies reporting circulating sCD40L levels in individuals with and without stable atherosclerosis. sCD40L levels were compared using random-effects meta-analysis, weighted by the inverse variance method (study protocol: PROSPERO CRD42020181392). RESULTS Fifty-four studies (59 estimates) including 7705 patients and 7841 controls were analyzed. sCD40L levels were found to be increased in patients with atherosclerosis, irrespective of the territory (standardized mean difference [SMD] 0.43, 95% CI 0.29-0.57; 59 estimates; χ2 heterogeneity p < 0.001; I2 = 92%). SMD was greatest in carotid atherosclerosis (SMD 0.58, 95% CI 0.30-0.86; 17 estimates), followed by coronary (SMD 0.43, 95% CI 0.24-0.62; 33 estimates), lower extremity (SMD 0.26, 95% CI -0.02-0.54; 7 estimates), and renal atherosclerosis (SMD -0.07, 95% CI -2.77-2.64; 2 estimates) (χ2 heterogeneity p < 0.001; I2 ≥ 80% for all). Subgroup analysis revealed that sCD40L levels were increased in clinical, but not subclinical, atherosclerosis. CONCLUSIONS sCD40L levels were increased in stable atherosclerosis, particularly in the carotid and coronary territories. These novel data support sCD40L as a marker of systemic atherosclerosis, possibly with differential roles in specific territories.
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22
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Liu W, Liu Y, Pan Z, Zhang X, Qin Y, Chen X, Li M, Chen X, Zheng Q, Liu X, Li D. Systematic Analysis of tRNA-Derived Small RNAs Discloses New Therapeutic Targets of Caloric Restriction in Myocardial Ischemic Rats. Front Cell Dev Biol 2020; 8:568116. [PMID: 33224944 PMCID: PMC7670042 DOI: 10.3389/fcell.2020.568116] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 10/01/2020] [Indexed: 12/23/2022] Open
Abstract
Caloric restriction (CR) is a novel dietary therapy that has a protective effect on myocardial ischemia. However, the mechanisms underlying the therapeutic effect of CR remain unclear. Transfer RNA-derived small RNAs (tsRNAs) are a novel type of short non-coding RNAs that have potential regulatory functions in various physiological and pathological processes. In this study, we explored new therapeutic targets of CR through tsRNA sequencing. Rats were randomly divided into three groups: a normal control group (norm group), isoproterenol (ISO)-induced myocardial ischemic group (MI group), and CR pretreatment plus ISO-induced myocardial ischemic group (CR + MI group). Triphenyl tetrazolium chloride staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, serum creatine kinase (CK) and lactic acid dehydrogenase activity detection kits, and creatine kinase isoenzyme 1 levels were used to measure the degree of myocardial ischemic injury. These indicators of myocardial ischemia were significantly improved in the CR + MI group compared with those in the MI group. In the ischemic myocardial tissue of the MI group, a total of 708 precisely matched tsRNAs were identified, and 302 tsRNAs (fold change >1.5, P < 0.05) were significantly changed when compared with those in the norm group. Furthermore, 55 tsRNAs were significantly regulated by CR pretreatment, among which five tsRNAs (tiRNA-His-GTG-004, tRF-Gly-TCC-018, tRF-Cys-GCA-022, tRF-Lys-CTT-026, tRF-Met-CAT-008) were randomly selected and verified by quantitative real-time polymerase chain reaction. In addition, predictions of target genes and bioinformatics analysis indicated that these tsRNAs may play a therapeutic role through the regulation of macromolecular metabolism. In conclusion, our findings reveal that tsRNAs are potential therapeutic targets for CR pre-pretreatment to improve myocardial ischemic injury. This study provides new ideas for future research on elucidating the mechanisms of CR pretreatment in ameliorating myocardial ischemic injury.
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Affiliation(s)
- Wenjing Liu
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Yang Liu
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Zhaohai Pan
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Xin Zhang
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Yao Qin
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Xiaojie Chen
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Minjing Li
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Xiaoyu Chen
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Qiusheng Zheng
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China.,Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, China
| | - Xiaona Liu
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
| | - Defang Li
- Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China
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23
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Pereira-da-Silva T, Napoleao P, Pinheiro T, Selas M, Silva F, Ferreira RC, Carmo MM. Inflammation is associated with the presence and severity of chronic coronary syndrome through soluble CD40 ligand. AMERICAN JOURNAL OF CARDIOVASCULAR DISEASE 2020; 10:329-339. [PMID: 33224580 PMCID: PMC7675147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Accepted: 09/02/2020] [Indexed: 06/11/2023]
Abstract
INTRODUCTION Inflammation contributes to the initiation and progression of atherosclerosis, although the underlying inflammatory pathways are not entirely known. Specifically, the role of the proinflammatory soluble CD40 ligand (sCD40L) on the expression of chronic coronary syndrome (CCS) is not completely understood. We evaluated whether sCD40L expression is associated with the presence of CCS and with the clinical and anatomical severity of CCS. METHODS We prospectively recruited 94 participants, assigned to two groups matched by age and sex, without coronary artery disease (n=26) and with CCS (n=68). Clinical, laboratory and anatomical data were prospectively collected, and serum levels of sCD40L were measured. RESULTS In patients with CCS, classic cardiovascular risk factors were more prevalent, and the sCD40L levels, leukocyte and neutrophil counts, and neutrophil/lymphocyte ratio, but not the C-reactive protein levels, were significantly higher than those in controls. sCD40L was independently associated with the presence of obstructive coronary artery disease in multivariate analysis. Regarding CCS severity, sCD40L levels showed a significant stepwise increase with increasing angina severity (ANOVA P=0.001). In addition, sCD40L was independently associated with the anatomical severity of coronary artery disease, as assessed by the Gensini score. Among patients with CCS, those with previous coronary artery bypass grafting (n=23) had lower sCD40L levels than patients waiting for revascularization (n=45) [4.3 (2.1) ng/mL vs. 6.8 (3.5) ng/mL, P=0.001]. CONCLUSIONS The expression of the proinflammatory sCD40L was associated with the presence of CCS and reflected the clinical and anatomical severity of CCS. In addition, we describe for the first time the association between prior CABG and reduced sCD40L levels in patients with CCS.
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Affiliation(s)
- Tiago Pereira-da-Silva
- Department of Cardiology, Hospital de Santa Marta, Centro Hospitalar Universitário de Lisboa CentralLisbon, Portugal
- NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de LisboaLisbon, Portugal
| | - Patricia Napoleao
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de LisboaLisbon, Portugal
| | - Teresa Pinheiro
- Instituto de Bioengenharia e Biociências, Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de LisboaLisbon, Portugal
| | - Mafalda Selas
- Department of Cardiology, Hospital de Santa Marta, Centro Hospitalar Universitário de Lisboa CentralLisbon, Portugal
| | - Filipa Silva
- Department of Cardiology, Hospital de Santa Marta, Centro Hospitalar Universitário de Lisboa CentralLisbon, Portugal
| | - Rui Cruz Ferreira
- Department of Cardiology, Hospital de Santa Marta, Centro Hospitalar Universitário de Lisboa CentralLisbon, Portugal
| | - Miguel Mota Carmo
- Chronic Diseases Research Center (CEDOC), NOVA Medical School/Faculdade de Ciências Médicas, Universidade NOVA de LisboaLisbon, Portugal
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24
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Shoaib M, Becker LB. A walk through the progression of resuscitation medicine. Ann N Y Acad Sci 2020; 1507:23-36. [PMID: 33040363 DOI: 10.1111/nyas.14507] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 09/03/2020] [Accepted: 09/14/2020] [Indexed: 01/11/2023]
Abstract
Cardiac arrest (CA) is a sudden and devastating disease process resulting in more deaths in the United States than many cancers, metabolic diseases, and even car accidents. Despite such a heavy mortality burden, effective treatments have remained elusive. The past century has been productive in establishing the guidelines for resuscitation, known as cardiopulmonary resuscitation (CPR), as well as developing a scientific field whose aim is to elucidate the underlying mechanisms of CA and develop therapies to save lives. CPR has been successful in reinitiating the heart after arrest, enabling a survival rate of approximately 10% in out-of-hospital CA. Although current advanced resuscitation methods, including hypothermia and extracorporeal membrane oxygenation, have improved survival in some patients, they are unlikely to significantly improve the national survival rate any further without a paradigm shift. Such a change is possible with sustained efforts in the basic and clinical sciences of resuscitation and their implementation. This review seeks to discuss the current landscape in resuscitation medicine-how we got here and where we are going.
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Affiliation(s)
- Muhammad Shoaib
- Department of Emergency Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.,The Feinstein Institutes for Medical Research, Manhasset, New York
| | - Lance B Becker
- Department of Emergency Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.,The Feinstein Institutes for Medical Research, Manhasset, New York.,Department of Emergency Medicine, North Shore University Hospital, Northwell Health, Manhasset, New York
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25
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Gomes WJ. Left main coronary artery stenosis: Evidence and pathophysiology. J Thorac Cardiovasc Surg 2020; 160:e179-e180. [PMID: 32680640 DOI: 10.1016/j.jtcvs.2020.05.102] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 05/19/2020] [Accepted: 05/20/2020] [Indexed: 10/23/2022]
Affiliation(s)
- Walter J Gomes
- Cardiovascular Surgery Discipline, Escola Paulista de Medicina and São Paulo Hospital, Federal University of São Paulo, São Paulo, Brazil
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26
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Ravikanth R. Role of 18F-FDG positron emission tomography in carotid atherosclerotic plaque imaging: A systematic review. World J Nucl Med 2020; 19:327-335. [PMID: 33623500 PMCID: PMC7875029 DOI: 10.4103/wjnm.wjnm_26_20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Revised: 04/03/2020] [Accepted: 04/14/2020] [Indexed: 12/22/2022] Open
Abstract
Stroke and other thromboembolic events in the brain are often due to carotid artery atherosclerosis, and atherosclerotic plaques with inflammation are considered particularly vulnerable, with an increased risk of becoming symptomatic. Positron emission tomography (PET) with 2-deoxy-2-[Fluorine-18] fluoro-D-glucose (18F-FDG) provides valuable metabolic information regarding arteriosclerotic lesions and may be applied for the detection of vulnerable plaque. At present, however, patients are selected for carotid surgical intervention on the basis of the degree of stenosis alone, and not the vulnerability or inflammation of the lesion. During the past decade, research using PET with the glucose analog tracer 18F-fluor-deoxy-glucose, has been implemented for identifying increased tracer uptake in symptomatic carotid plaques, and tracer uptake has been shown to correlate with plaque inflammation and vulnerability. These findings imply that 18F-FDG PET might hold the promise for a new and better diagnostic test to identify patients eligible for carotid endarterectomy. The rationale for developing diagnostic tests based on molecular imaging with 18F-FDG PET, as well as methods for simple clinical PET approaches, are discussed. This is a systematic review, following Preferred Reporting Items for Systematic Reviews guidelines, which interrogated the PUBMED database from January 2001 to November 2019. The search combined the terms, “atherosclerosis,” “inflammation,” “FDG,” and “plaque imaging.” The search criteria included all types of studies, with a primary outcome of the degree of arterial vascular inflammation determined by 18F-FDG uptake. This review examines the role of 18F-FDG PET imaging in the characterization of atherosclerotic plaques.
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Affiliation(s)
- Reddy Ravikanth
- Department of Radiology, St. John's Hospital, Kattappana, Kerala, India
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27
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Bt Hj Idrus R, Sainik NQAV, Nordin A, Saim AB, Sulaiman N. Cardioprotective Effects of Honey and Its Constituent: An Evidence-Based Review of Laboratory Studies and Clinical Trials. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E3613. [PMID: 32455701 PMCID: PMC7277934 DOI: 10.3390/ijerph17103613] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 05/09/2020] [Accepted: 05/09/2020] [Indexed: 12/19/2022]
Abstract
Cardiovascular disease is a major public health burden worldwide. Myocardial infarction is the most common form of cardiovascular disease resulting from low blood supply to the heart. It can lead to further complications such as cardiac arrhythmia, toxic metabolite accumulation, and permanently infarcted areas. Honey is one of the most prized medicinal remedies used since ancient times. There is evidence that indicates honey can function as a cardioprotective agent in cardiovascular diseases. The present review compiles and discusses the available evidence on the effect of honey on cardiovascular diseases. Three electronic databases, namely, PubMed, Scopus, and MEDLINE via EBSCOhost, were searched between January 1959 and March 2020 to identify reports on the cardioprotective effect of honey. Based on the pre-set eligibility criteria, 25 qualified articles were selected and discussed in this review. Honey investigated in the studies included varieties according to their geological origin. Honey protects the heart via lipid metabolism improvement, antioxidative activity, blood pressure modulation, heartbeat restoration, myocardial infarct area reduction, antiaging properties, and cell apoptosis attenuation. This review establishes honey as a potential candidate to be explored further as a natural and dietary alternative to the management of cardiovascular disease.
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Affiliation(s)
- Ruszymah Bt Hj Idrus
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur 56000, Malaysia; (R.B.H.I.); (A.N.)
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia;
| | | | - Abid Nordin
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur 56000, Malaysia; (R.B.H.I.); (A.N.)
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia;
| | - Aminuddin Bin Saim
- Ear, Nose & Throat Consultant Clinic, Ampang Puteri Specialist Hospital, Ampang, Selangor 68000, Malaysia;
| | - Nadiah Sulaiman
- Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur 56000, Malaysia; (R.B.H.I.); (A.N.)
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28
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Zhang H, Chen L, Sun X, Yang Q, Wan L, Guo C. Matrine: A Promising Natural Product With Various Pharmacological Activities. Front Pharmacol 2020; 11:588. [PMID: 32477114 PMCID: PMC7232545 DOI: 10.3389/fphar.2020.00588] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 04/16/2020] [Indexed: 12/30/2022] Open
Abstract
Matrine is an alkaloid isolated from the traditional Chinese medicine Sophora flavescens Aiton. At present, a large number of studies have proved that matrine has an anticancer effect can inhibit cancer cell proliferation, arrest cell cycle, induce apoptosis, and inhibit cancer cell metastasis. It also has the effect of reversing anticancer drug resistance and reducing the toxicity of anticancer drugs. In addition, studies have reported that matrine has a therapeutic effect on Alzheimer's syndrome, encephalomyelitis, asthma, myocardial ischemia, rheumatoid arthritis, osteoporosis, and the like, and its mechanism is mainly related to the inhibition of inflammatory response and apoptosis. Its treatable disease spectrum spans multiple systems such as the nervous system, circulatory system, and immune system. The antidisease effect and mechanism of matrine are diverse, so it has high research value. This review summarizes recent studies on the pharmacological mechanism of matrine, with a view to providing reference for subsequent research.
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Affiliation(s)
- Hong Zhang
- Department of Pharmacy, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.,School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Linlin Chen
- Department of Pharmacy, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.,School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xipeng Sun
- Department of Pharmacy, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Quanjun Yang
- Department of Pharmacy, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Lili Wan
- Department of Pharmacy, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Cheng Guo
- Department of Pharmacy, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.,School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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29
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Tang Q, Cao Y, Xiong W, Ke X, Zhang J, Xia Y, Liu D. Glycyrrhizic acid exerts protective effects against hypoxia/reoxygenation-induced human coronary artery endothelial cell damage by regulating mitochondria. Exp Ther Med 2020; 20:335-342. [PMID: 32509013 PMCID: PMC7271712 DOI: 10.3892/etm.2020.8668] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 03/05/2020] [Indexed: 01/01/2023] Open
Abstract
Hypoxia/reoxygenation (H/R) is one of the main causes of coronary artery disease (CAD), which is primarily induced by damage to coronary artery endothelial cells (CAECs). Glycyrrhizic acid (GA) is a natural and abundant pentacyclic triterpenoid glycoside of the licorice root extract, and it has been reported to elicit protective effects against hypoxia, inflammation and apoptosis in ischemic myocardium; therefore, GA may serve as a promising therapeutic agent for ischemia-associated CAD. In the present study, the protective effects of GA against H/R-induced injury in CAECs were investigated. Treatment with GA during H/R maintained cell viability and decreased H/R-induced cell apoptosis in human CAECs. In addition, H/R-mediated induction of intracellular and mitochondrial reactive oxygen species (ROS) was significantly decreased by GA exposure. Similar to ROS scavengers, GA treatment not only exhibited protective effects, but also maintained the mitochondrial membrane potential after H/R and inhibited H/R-induced mitochondrial dysfunction, including deficits in ATP synthesis, mitochondrial DNA copy number and mitochondrial transcriptional activity. Furthermore, GA decreased autophagy/mitophagy, and its protective effect against H/R was abolished by autophagy promotion. Collectively, the results suggested that GA exhibited protective effects against H/R-induced CAEC injury by decreasing ROS accumulation and maintaining mitochondrial homeostasis. Further investigation into the precise mechanisms underlying the decrease in ROS accumulation induced by GA is required.
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Affiliation(s)
- Quan Tang
- Department of Imaging, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Yuping Cao
- Department of Imaging, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Wei Xiong
- Department of Cardiac Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Xixian Ke
- Department of Cardiac Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Jian Zhang
- Department of Cardiac Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Yu Xia
- Department of Cardiac Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
| | - Daxing Liu
- Department of Cardiac Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
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30
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Carbajal-García A, Reyes-García J, Montaño LM. Androgen Effects on the Adrenergic System of the Vascular, Airway, and Cardiac Myocytes and Their Relevance in Pathological Processes. Int J Endocrinol 2020; 2020:8849641. [PMID: 33273918 PMCID: PMC7676939 DOI: 10.1155/2020/8849641] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 09/17/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION Androgen signaling comprises nongenomic and genomic pathways. Nongenomic actions are not related to the binding of the androgen receptor (AR) and occur rapidly. The genomic effects implicate the binding to a cytosolic AR, leading to protein synthesis. Both events are independent of each other. Genomic effects have been associated with different pathologies such as vascular ischemia, hypertension, asthma, and cardiovascular diseases. Catecholamines play a crucial role in regulating vascular smooth muscle (VSM), airway smooth muscle (ASM), and cardiac muscle (CM) function and tone. OBJECTIVE The aim of this review is an updated analysis of the role of androgens in the adrenergic system of vascular, airway, and cardiac myocytes. Body. Testosterone (T) favors vasoconstriction, and its concentration fluctuation during life stages can affect the vascular tone and might contribute to the development of hypertension. In the VSM, T increases α1-adrenergic receptors (α 1-ARs) and decreases adenylyl cyclase expression, favoring high blood pressure and hypertension. Androgens have also been associated with asthma. During puberty, girls are more susceptible to present asthma symptoms than boys because of the increment in the plasmatic concentrations of T in young men. In the ASM, β 2-ARs are responsible for the bronchodilator effect, and T augments the expression of β 2-ARs evoking an increase in the relaxing response to salbutamol. The levels of T are also associated with an increment in atherosclerosis and cardiovascular risk. In the CM, activation of α 1A-ARs and β 2-ARs increases the ionotropic activity, leading to the development of contraction, and T upregulates the expression of both receptors and improves the myocardial performance. CONCLUSIONS Androgens play an essential role in the adrenergic system of vascular, airway, and cardiac myocytes, favoring either a state of health or disease. While the use of androgens as a therapeutic tool for treating asthma symptoms or heart disease is proposed, the vascular system is warmly affected.
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Affiliation(s)
- Abril Carbajal-García
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, Mexico
| | - Jorge Reyes-García
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, Mexico
| | - Luis M. Montaño
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, CDMX, Mexico
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