Hydrogen sulfide revisited: a stealthy ally in the unseen war against cardiovascular disease.

Hydrogen sulfide (H2S), an endogenously produced gaseous signaling molecule, plays a pivotal role in cardiovascular physiology and pathology. In the cardiovascular system, H2S is extensively involved in regulating a wide range of key cellular processes critical for maintaining cardiovascular health. Maintaining H2S homeostasis is essential for cardiovascular health, and disruptions in its biosynthesis or signaling are implicated in the onset and progression of cardiovascular diseases (CVDs) such as atherosclerosis, heart failure, myocardial infarction, ischemia/reperfusion injury, stroke, cardiac hypertrophy, and fibrosis. Restoring H2S balance, either by stimulating endogenous production or through the administration of exogenous H2S donors, has shown considerable therapeutic potential in CVD management. In this review, we comprehensively summarize the essential functions of H2S, examine H2S-mediated cellular and pathophysiological processes within the cardiovascular system, including oxidative stress, mitochondrial function, inflammation, cellular senescence, cell death, proliferation, autophagy, calcium channels, calcium homeostasis, and glucose/lipid metabolism, and elucidate the underlying molecular mechanisms contributing to various CVDs. Additionally, we discuss recent progress in H2S-based therapeutic strategies and their associated challenges, aiming to provide a thorough understanding of H2S as a novel therapeutic target in CVDs.