H2S therapy with SG-1002 resulted in cardioprotection in the setting of pressure overload-induced heart failure via upregulation of the VEGF-Akt-eNOS-NO-cyclic guanosine monophosphate (cGMP) pathway with preserved mitochondrial function, attenuated oxidative stress, and increased myocardial vascular density. The gene discussed is NOS3; the disease is heart failure.