Role of Cystathionine γ-Lyase/Hydrogen Sulfide Pathway in Cardiovascular Disease: A Novel Therapeutic Strategy?

Significance: Hydrogen sulfide (H2S) has traditionally been considered a toxic environmental pollutant. In the late 1990s, the presumed solely harmful role of H2S has been challenged because H2S may also be involved in the maintenance and preservation of cardiovascular homeostasis. Recent Advances: The production of endogenous H2S has been attributed to three key enzymes, cystathionine gamma-lyase (CSE), cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase. The recognition of H2S 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/H2S pathway, such as atherosclerosis, myocardial infarction, hypertension, and shock. Critical Issues: Many biological activities and molecular mechanisms of H2S in the cardiovascular system have been demonstrated in studies using different tools, such as the genetic overexpression of CSE, the direct administration of H2S donors, or the use of H2S-releasing pro-drugs. Unfortunately, the role of the CSE/H2S 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/H2S pathway may provide potential therapeutic targets for treating cardiovascular disorders. But the molecular targets of H2S still need to be identified. Antioxid. Redox Signal. 17, 106-118.