Hydrogen sulfide provides cardioprotection against myocardial/ischemia reperfusion injury in the diabetic state through the activation of the RISK pathway

• Type of Material: Article
• Authors: Jonathan P Lambert, Emory University; Chad K Nicholson, Emory University; Hena Amin, Emory University; Sana Amin, Emory University; John Calvert, Emory University
• Language: English
• Date: 2014-12-12
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Lambert et al.; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13618-014-0020-0
• Title of Journal or Parent Work: Medical Gas Research
• ISSN: 2045-9912
• Volume: 4
• Issue: 1
• Start Page: 20
• End Page: 20
• Grant/Funding Information: This work was also supported by funding from the Carlyle Fraser Heart Center of Emory University Hospital Midtown.; Supported by a grant the National Institutes of Health National Heart Lung and Blood Institute (5R01HL098481-05) to J.W.C.
• Keywords: RISK pathway; Diabetes; Cardioprotection; Hydrogen sulfide; Myocardial Ischemia-reperfusion injury
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Rehabilitation and Therapy

Abstract

Background Coronary artery disease remains the principal cause of death in patients with diabetes mellitus. Diabetic mice display exacerbated injury following myocardial ischemia-reperfusion (MI/R) and are resistant to most therapeutic interventions. We have reported that sodium sulfide (Na2S) therapy confers cardioprotection during MI/R in non-diabetic mice. Here we tested the hypothesis that Na2S therapy would limit the extent of myocardial injury following MI/R when administered at the time of reperfusion. Methods and results Diabetic mice (db/db, 12 weeks of age) were subjected to transient myocardial ischemia for a period of 30 minutes followed by reperfusion up to 24 hours. Na2S (0.05 to 1 mg/kg) or saline (vehicle) was administered into the left ventricular lumen at the time of reperfusion. Na2S therapy significantly decreased myocardial injury in the db/db diabetic mouse, as evidenced by a reduction in infarct size and circulating troponin-I levels. The reduction in myocardial injury was also associated with a reduction in oxidative stress and a decrease in cleaved caspase-3 expression. In an effort to evaluate the signaling mechanism responsible for the observed cardioprotection, additional groups of mice were sacrificed during early reperfusion. Hearts were excised and processed for Western blot analysis. These studies revealed that Na2S therapy activated the Erk1/2 arm of the Reperfusion Injury Salvage Kinase (RISK) pathway. Conclusion These findings provide important information that myocardial Erk1/2 activation by Na2S therapy following MI/R sets into motion events, which ultimately lead to cardioprotection in the setting of diabetes.