Protective mechanisms of hydrogen sulfide in myocardial ischemia.

Hydrogen sulfide (H S), which has been identified as the third gaseous signaling molecule after nitric oxide (NO) and carbon monoxide (CO), plays an important role in maintaining homeostasis in the cardiovascular system. Endogenous H S is produced mainly by three endogenous enzymes: cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfur transferase. Numerous studies have shown that H S has a significant protective role in myocardial ischemia. The mechanisms by which H S affords cardioprotection include the antifibrotic and antiapoptotic effects, regulation of ion channels, protection of mitochondria, reduction of oxidative stress and inflammatory response, regulation of microRNA expression, and promotion of angiogenesis. Amplification of NO- and CO-mediated signaling through crosstalk between H S, NO, and CO may also contribute to the cardioprotective effect. Exogenous H S donors are expected to become effective drugs for the treatment of cardiovascular diseases. This review article focuses on the protective mechanisms and potential therapeutic applications of H S in myocardial ischemia.