Hydrogen sulfide and the pathogenesis of atherosclerosis

Significance: Stigmatized as a toxic environmental pollutant for centuries, hydrogen sulfide (H₂S) has gained recognition over the last decade as an important gasotransmitter that functions in physiological and pathophysiological conditions, such as atherosclerosis. Recent Advances: Atherosclerosis is a common disease that stems from the buildup of fatty/cholesterol plaques on the endothelial cells of arteries. The deposits mitigate thickening and stiffening of arterial tissue, which contributes to concomitant systemic or localized vascular disorders. Recently, it has been recognized that H₂S plays an anti-atherosclerotic role, and its deficiency leads to early development and progression of atherosclerosis. This review article presents multiple lines of evidence for the protective effects of H₂S against the development of atherosclerosis. Also highlighted are the characterization of altered metabolism of H₂S in the development of atherosclerosis, underlying molecular and cellular mechanisms, and potential therapeutic intervention based on H₂S supplementation for atherosclerosis management. Critical Issues: Although a protective role of H₂S against atherosclerosis has emerged, controversy remains regarding the mechanisms underlying H₂S-induced endothelial cell proliferation and angiogenesis as well as its anti-inflammatory properties. The therapeutic value of H₂S to this pathophysiological condition has not been tested clinically but, nonetheless, it shows tremendous promise. Future Directions: The efficiency and safety profile of H₂S-based therapeutic approaches should be refined, and the mechanisms by which H ₂S exerts its beneficial effects should be elucidated to develop more specific and potent therapeutic strategies to treat atherosclerosis. Whether the therapeutic effects of H₂S in animal studies are transferable to clinical studies merits future investigation. Antioxid. Redox Signal. 20, 805-817.