Role of cystathionine γ-lyase/hydrogen sulfide pathway in cardiovascular disease: a novel therapeutic strategy?

SIGNIFICANCE: Hydrogen sulfide (H(2)S) has traditionally been considered a toxic environmental pollutant. In the late 1990s, the presumed solely harmful role of H(2)S has been challenged because H(2)S may also be involved in the maintenance and preservation of cardiovascular homeostasis. RECENT ADVANCES: The production of endogenous H(2)S has been attributed to three key enzymes, cystathionine γ-lyase (CSE), cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase. The recognition of H(2)S as the third gaseous signaling molecule has stimulated research on a multitude of pathophysiologic events in the cardiovascular system. In particular, important roles in cardiovascular disorder processes are ascribed to the CSE/H(2)S pathway, such as atherosclerosis, myocardial infarction, hypertension, and shock. CRITICAL ISSUES: Many biological activities and molecular mechanisms of H(2)S in the cardiovascular system have been demonstrated in studies using different tools, such as the genetic overexpression of CSE, the direct administration of H(2)S donors, or the use of H(2)S-releasing pro-drugs. Unfortunately, the role of the CSE/H(2)S pathway in cardiovascular disease remains controversial in numerous areas, and many questions regarding the gaseous molecule still remain unanswered. FUTURE DIRECTIONS: Advances in basic research indicate that the CSE/H(2)S pathway may provide potential therapeutic targets for treating cardiovascular disorders. But the molecular targets of H(2)S still need to be identified.