Abstract 15549: Hydrogen Sulfide Attenuates Cardiac Dysfunction Following Pressure Overload Induced Hypertrophy and Heart Failure Via Augmentation of Angiogenesis
Introduction: Hydrogen sulfide (H2S) upregulates anti-oxidants, anti-apoptosis, promotes angiogenesis, and cellular survival. H2S plays an extremely important role in the homeostasis of the cardiovascular system and in the pathogenesis of cardiovascular disease. Chronic hypertension induces cardiac hypertrophy to preserve cardiac function but leads to progressive cardiac dysfunction from cardiac dilation and loss of contractility. The aim of the present study was to investigate whether H2S therapy attenuates myocardial injury in the setting of pressure overload induced heart failure.
Methods: Transverse aortic constriction (TAC) surgery was performed in C57/BL6J mice (12-14 weeks old, n=15-20/group) to create pressure overload and cardiac hypertrophy. Before TAC, basal echocardiography was performed. Mice were divided into two groups post-operative day 1; H2S donor (diallyl trisulfide; DATS 100 μ g/kg twice daily i.p.) group or 1% DMSO (i.p.) group (VEH). Follow-up echocardiography was performed up to 6 weeks and heart tissue was obtained.
Results: After 3 weeks of TAC procedure, left ventricular (LV) wall obtained equivalent cardiac hypertrophy in both groups (VEH; 1.22 mm vs. DATS; 1.18 mm, p=NS). However, DATS treatment significantly attenuated LV cavity dilation (LVEDD/LVESD; 3.53/2.39 mm vs. 3.90/3.03 mm, p < 0.05) and LV contractility (EF; 62% vs. 45%, p < 0.001) after 6 weeks of TAC compared to VEH mice. Moreover, DATS treatment significantly increased myocardial tissue phosphorylation of eNOS at Ser-1177 (p < 0.01 vs. VEH) and decreased phosphorylation of eNOS at Thr-495 (p < 0.01 vs. VEH). Moreover, vascular endothelial growth factor-A (VEGF-A) protein levels were significantly increased in DATS treated heart (p < 0.01 vs. VEH).
Conclusion: Our results indicate H2S prevented transition from compensated to decompensated cardiac hypertrophy induced heart failure with decreased LV dilatation and improved left ventricular EF. H2S treatment might increase myocardial vasculogeneis via increased VEGF-eNOS signaling to improve myocardial perfusion and cardiac function.
- © 2011 by American Heart Association, Inc.