Figure 7.

Schematic diagram highlighting the proposed mechanism by which cystathionine gama lyase (CSE) or exogenous hydrogen sulfide protects the heart following transverse aortic constriction (TAC). Our data suggest (CSE) or hydrogen suflide donor therapy with SG-1002 activates vascular endothelial growth factor (VEGF) and subsequently phosphorylates Akt. Akt activation results in phosphorylation and activation of eNOS. Following eNOS activation nitric oxide (NO) and nitrite (NO₂) bioavailability are increased in conjunction with increases in myocardial cGMP. These molecular signals result in reduced myocardial oxidative stress and injury, improvements in mitochondrial respiration, and decreased cardiac fibrosis. Ultimately, these cytoprotective actions prevent the transition from compensated to decompensated heart failure and left ventricular (LV) ejection fraction is preserved.