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Journal of Cardiovascular Pharmacology... May 2017Myocardial ischemia/reperfusion injury represents a major threat to human health and contributes to adverse cardiovascular outcomes worldwide. Despite the identification... (Review)
Review
Myocardial ischemia/reperfusion injury represents a major threat to human health and contributes to adverse cardiovascular outcomes worldwide. Despite the identification of numerous molecular mechanisms, understanding of the complex pathophysiology of this clinical syndrome remains incomplete. Thioredoxin-interacting protein (Txnip) has been of great interest in the past decade since it has been reported to be a critical regulator in human diseases with several important cellular functions. Thioredoxin-interacting protein binds to and inhibits thioredoxin, a redox protein that neutralizes reactive oxygen species (ROS), and through its interaction with thioredoxin, Txnip sensitizes cardiomyocytes to ROS-induced apoptosis. Interestingly, evidence from recent studies also suggests that some of the effects of Txnip may be unrelated to changes in thioredoxin activity. These pleiotropic effects of Txnip are mediated by interactions with other signaling molecules, such as nod-like receptor pyrin domain-containing 3 inflammasome and glucose transporter 1. Indeed, Txnip has been implicated in the regulation of inflammatory response and glucose homeostasis during myocardial ischemia/reperfusion injury. This review attempts to make the case that in addition to interacting with thioredoxin, Txnip contributes to some of the pathological consequences of myocardial ischemia and infarction through endogenous signals in multiple molecular mechanisms.
Topics: Animals; Apoptosis; Carrier Proteins; Glucose; Humans; Inflammation Mediators; MicroRNAs; Myocardial Reperfusion Injury; Myocardium; Oxidative Stress; Reactive Oxygen Species; Signal Transduction
PubMed: 27807222
DOI: 10.1177/1074248416675731 -
Journal of Cardiovascular Pharmacology... Nov 2021Vascular stiffness and endothelial dysfunction are accelerated by acute myocardial infarction (AMI) and subsequently increase the risk for recurrent coronary events.
BACKGROUND
Vascular stiffness and endothelial dysfunction are accelerated by acute myocardial infarction (AMI) and subsequently increase the risk for recurrent coronary events.
AIM
To explore whether remote ischemic perconditioning (RIPerc) protects against coronary and aorta endothelial dysfunction as well as aortic stiffness following AMI.
METHODS
Male OFA-1 rats were subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by reperfusion either 3 or 28 days with or without RIPerc. Three groups: (1) sham operated (Sham, without LAD occlusion); (2) myocardial ischemia and reperfusion (MIR) and (3) MIR + RIPerc group with 3 cycles of 5 minutes of IR on hindlimb performed during myocardial ischemia were used. Assessment of vascular reactivity in isolated septal coronary arteries (non-occluded) and aortic rings as well as aortic stiffness was assessed by wire myography either 3 or 28 days after AMI, respectively. Markers of pro-inflammatory cytokines, adhesion molecules were assessed by RT-qPCR and ELISA.
RESULTS
MIR promotes impaired endothelial-dependent relaxation in septal coronary artery segments, increased aortic stiffness and adverse left ventricular remodeling. These changes were markedly attenuated in rats treated with RIPerc and associated with a significant decline in P-selectin, IL-6 and TNF-α expression either in infarcted or non-infarcted myocardial tissue samples.
CONCLUSIONS
Our study for the first time demonstrated that RIPerc alleviates MIR-induced coronary artery endothelial dysfunction in non-occluded artery segments and attenuates aortic stiffness in rats. The vascular protective effects of RIPerc are associated with ameliorated inflammation and might therefore be caused by reduced inflammatory signaling.
Topics: Animals; Coronary Vessels; Cytokines; Inflammation; Ischemic Preconditioning, Myocardial; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Rats; Vascular Stiffness
PubMed: 34342526
DOI: 10.1177/10742484211031327 -
Journal of Molecular and Cellular... Apr 2015
Topics: Animals; Cardiotonic Agents; Carrier Proteins; Humans; Male; Myocardial Reperfusion Injury; Recombinant Proteins
PubMed: 25655937
DOI: 10.1016/j.yjmcc.2015.01.023 -
Journal of the American College of... Feb 2015
Topics: Animals; Edema; Male; Myocardial Reperfusion Injury
PubMed: 25461691
DOI: 10.1016/j.jacc.2014.11.006 -
Cell Cycle (Georgetown, Tex.) Feb 2021This project aimed to investigate the protective mechanism of sufentanil pretreatment on myocardial ischemia-reperfusion injury (IRI). An rat model of myocardial IRI...
This project aimed to investigate the protective mechanism of sufentanil pretreatment on myocardial ischemia-reperfusion injury (IRI). An rat model of myocardial IRI and an cultured cardiomyocyte model of hypoxia-reoxygenation (H/R) were used to confirm the anti-oxidation and anti-autophagy effects of sufentanil. The interaction between miR-125a and damage-regulated autophagy regulator 2 (DRAM2) was verified by luciferase reporter assay. We showed that pretreatment with sufentanil suppressed myocardial damage caused by IRI in rats by inhibiting oxidative stress and mitochondrial autophagy. Furthermore, the cardioprotective mechanism of sufentanil was mediated by miR-125a. MiR-125a targeted DRAM2 to ameliorate cardiomyocyte autophagy and oxidative injury following H/R treatment. In conclusion, our results demonstrated that sufentanil pretreatment produced a protective effect against myocardial IRI via regulating miR-125a/DRAM2 signaling axis.
Topics: Animals; Cardiotonic Agents; Cell Line, Transformed; Ischemic Preconditioning, Myocardial; Male; Membrane Proteins; MicroRNAs; Myocardial Reperfusion Injury; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; Sufentanil
PubMed: 33475463
DOI: 10.1080/15384101.2021.1875668 -
Hellenic Journal of Cardiology : HJC =... 2016
Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Diabetes Complications; Diabetes Mellitus; Humans; Meta-Analysis as Topic; Myocardial Infarction; Myocardial Reperfusion; Platelet Aggregation Inhibitors; Risk Factors
PubMed: 28302514
DOI: 10.1016/j.hjc.2016.12.012 -
Journal of the American Heart... Jun 2020Ischemia/reperfusion injury is a complex molecular cascade that causes deleterious cellular damage and organ dysfunction. Stroke, sudden cardiac arrest, and acute... (Review)
Review
Ischemia/reperfusion injury is a complex molecular cascade that causes deleterious cellular damage and organ dysfunction. Stroke, sudden cardiac arrest, and acute myocardial infarction are the most common causes of ischemia/reperfusion injury without effective pharmacologic therapies. Existing preclinical evidence suggests that histone deacetylase inhibitors may be an efficacious, affordable, and clinically feasible therapy that can improve neurologic and cardiac outcomes following ischemia/reperfusion injury. In this review, we discuss the pathophysiology and epigenetic modulations of ischemia/reperfusion injury and focus on the neuroprotective and cardioprotective effects of histone deacetylase inhibitors. We also summarize the protective effects of histone deacetylase inhibitors for other vital organs and highlight the key research priorities for their successful translation to the bedside.
Topics: Animals; Brain; Cardiovascular Agents; Cerebrovascular Circulation; Coronary Circulation; Epigenesis, Genetic; Histone Deacetylase Inhibitors; Humans; Myocardial Reperfusion Injury; Myocardium; Neuroprotective Agents; Reperfusion Injury
PubMed: 32441201
DOI: 10.1161/JAHA.120.016349 -
Circulation Journal : Official Journal... Jun 2017
Topics: Humans; Hydrogen; Myocardial Infarction; Myocardial Reperfusion; Translational Research, Biomedical
PubMed: 28566655
DOI: 10.1253/circj.CJ-17-0520 -
Journal of the American College of... Aug 2020Myocardial damage due to acute ST-segment elevation myocardial infarction (STEMI) remains a significant global health problem. New approaches to limit myocardial infarct...
BACKGROUND
Myocardial damage due to acute ST-segment elevation myocardial infarction (STEMI) remains a significant global health problem. New approaches to limit myocardial infarct size and reduce progression to heart failure after STEMI are needed. Mechanically reducing left ventricular (LV) workload (LV unloading) before coronary reperfusion is emerging as a potential approach to reduce infarct size.
OBJECTIVES
Given the central importance of mitochondria in reperfusion injury, we hypothesized that compared with immediate reperfusion (IR), LV unloading before reperfusion improves myocardial energy substrate use and preserves mitochondrial structure and function.
METHODS
To explore the effect of LV unloading duration on infarct size, we analyzed data from the STEMI-Door to Unload (STEMI-DTU) trial and then tested the effect of LV unloading on ischemia and reperfusion injury, cardiac metabolism, and mitochondrial function in swine models of acute myocardial infarction.
RESULTS
The duration of LV unloading before reperfusion was inversely associated with infarct size in patients with large anterior STEMI. In preclinical models, LV unloading reduced the expression of hypoxia-sensitive proteins and myocardial damage due to ischemia alone. LV unloading with a transvalvular pump (TV-P) but not with venoarterial extracorporeal membrane oxygenation (ECMO) reduced infarct size. Using unbiased and blinded metabolic profiling, TV-P improved myocardial energy substrate use and preserved mitochondrial structure including cardiolipin content after reperfusion compared with IR or ECMO. Functional testing in mitochondria isolated from the infarct zone showed an intact mitochondrial structure including cardiolipin content, preserved activity of the electron transport chain including mitochondrial complex I, and reduced oxidative stress with TV-P-supported reperfusion but not with IR or ECMO.
CONCLUSIONS
These novel findings identify that transvalvular unloading limits ischemic injury before reperfusion, improves myocardial energy substrate use, and preserves mitochondrial structure and function after reperfusion.
Topics: Animals; Heart Valves; Heart Ventricles; Heart-Assist Devices; Male; Myocardial Reperfusion; Preoperative Care; ST Elevation Myocardial Infarction; Swine
PubMed: 32762903
DOI: 10.1016/j.jacc.2020.06.031 -
PloS One 2014The protective role of etanercept in myocardial ischemia/reperfusion is not well understood. The aim of this study was to investigate whether etanercept modulates...
The protective role of etanercept in myocardial ischemia/reperfusion is not well understood. The aim of this study was to investigate whether etanercept modulates neutrophil accumulation, TNF-α induction and oxidative stress in an ischemia/reperfusion injured rat heart model. Rats were randomly exposed to sham operation, myocardial ischemia/reperfusion (MI/R) alone, MI/R+ etanercept. The results demonstrated that compared to MI/R, etanercept reduced myocardial infarction area, myocardial myeloperoxidase (MPO) levels, serum creatinine kinase (CK) and lactate dehydrogenase (LDH) levels, and both serum and myocardial TNF-α production. Etanercept also markedly enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reduced the level of malondialdehyde (MDA) in MI/R rats. In summary, our data suggested that etanercept has protective effects against MI/R injury in rats, which may be attributed to attenuating inflammation and oxidative stress.
Topics: Animals; Apoptosis; Creatine Kinase, MB Form; Disease Models, Animal; Etanercept; Gene Expression Regulation; Glutathione Peroxidase; Immunoglobulin G; Inflammation; Lactate Dehydrogenases; Male; Malondialdehyde; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Neutrophil Infiltration; Oxidative Stress; Rats; Receptors, Tumor Necrosis Factor; Superoxide Dismutase; Toll-Like Receptor 4; Troponin I; Tumor Necrosis Factor-alpha; Ventricular Dysfunction
PubMed: 25260027
DOI: 10.1371/journal.pone.0108024