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.