GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats.

Meng Guoliang,Shan Liyang,Xiao Yujiao,Xie Liping,Wang Jing,Bai Wenli,Ji Yong,K Philip

doi:10.7555/jbr.28.20140037

Abstract

Hydrogen sulfide (H2S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to determine the protective effect of slow-releasing H2S donor GYY4137 on myocardial ischemia and reperfusion (I/R) injury and to investigate the possible signaling mechanisms involved. Male Sprague-Dawley rats were treated with GYY4137 at 12.5 mg/(kg·day), 25 mg/(kg·day) or 50 mg/(kg·day) intraperitoneally for 7 days. Then, rats were subjected to 30 minutes of left anterior descending coronary artery occlusion followed by reperfusion for 24 hours. We found that GYY4137 increased the cardiac ejection fraction and fractional shortening, reduced the ischemia area, alleviated histological injury and decreased plasma creatine kinase after myocardial I/R. Both H2S concentration in plasma and cystathionine-γ-lyase (CSE) activity in the myocardium were enhanced in the GYY4137 treated groups. GYY4137 also decreased malondialdehyde and myeloperoxidase levels in serum, attenuated superoxide anion level and suppressed phosphorylation of mitogen activated protein kinases in the myocardium after I/R. Meanwhile, GYY4137 increased the expression of Bcl-2 but decreased the expression of Bax, caspase-3 activity and apoptosis in the myocardium. The data suggest that GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis.

Highlights

Acute coronary artery diseases are one of the leading causes of mortality and morbidity worldwide
Cardiac reperfusion after an acute myocardial infarction episode usually contributes to myocyte damage, which is named as myocardial ischemia and nThese authors contributed to this work. * Corresponding author: Yong Ji, MD, PhD, Key Laboratory of Cardiovascular Disease and Molecular Intervention, State Key Laboratory of Reproductive Medicine, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing, Jiangsu 210029, China
Thirty minutes of ischemia followed by 24 hours of reperfusion decreased the Ejection fraction (EF) and fractional shortening (FS) in vehicle-treated rats compared to the sham-operated rats

Summary

Introduction

Acute coronary artery diseases are one of the leading causes of mortality and morbidity worldwide. CSE is the major hydrogen sulfide generating enzyme in the cardiovascular system, especially in the heart, vascular and smooth muscle cells, while CBS is expressed in the brain and nervous system, and 3-MST is present in the mitochondrials of the liver, kidney, brain and vascular cells[5,6]. Johansen et al reported that the perfusion of NaHS reduces myocardial infarction size in the Langendorff-perfused heart after 30 minutes of left main coronary artery occlusion and 120 minutes of reperfusion[9]. CSE inhibitor significantly increased the infarct size due to myocardial ischemia[10,11], while heart-specific overexpression of CSE significantly limited the infarct size due to left coronary artery occlusion for 45 minutes followed by reperfusion for 72 hours[12]. In the isolated perfused heart, H2S improves the heart mechanics after I/R injury[16]

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Results

Conclusion