Hydrogen sulfide donors: Therapeutic potential in anti-atherosclerosis

Atherosclerosis (AS), an important cause of high mortality of cardiovascular disease, involves numerous pathophysiological processes, including endothelial cell damage, oxidative stress, inflammation, lipid deposition, vascular smooth muscle proliferation and migration, macrophage-derived foam cell formation, and platelet aggregation, and seriously endangers human health and safe of life. Hydrogen sulfide (H₂S) was discovered as the third gaseous signaling molecule following nitric oxide (NO) and carbon monoxide (CO), and has been proposed to exert potentially significant effects in many physiological processes, especially in atherosclerosis. Compelling evidence suggests that malfunction of CSE/H₂S pathway and downregulation of endogenous H₂S level contribute to the pathogenesis of atherosclerosis, whereas exogenous supplementation of H₂S can ameliorate many of atherogenic processes. The current knowledge on the anti-atherogenic role of H₂S comes from the use of H₂S donors and CSE or CBS inhibitors, or another more accurate genetic technology, including gene knockout and gene therapy studies. Among them H₂S releasing donors have vast therapeutic potential in anti-atherosclerosis and are promising as one of the clinical strategies for atherosclerosis treatment. Based on the recent studies on therapeutic effects and mechanisms of H₂S donors, this review focuses on the most recent advances of therapeutic potential of H₂S donors in anti-atherosclerosis, especially synthetic organic donors, because sulfide salts can release H₂S rapidly and lead to various adverse effects. In addition, the future of this domain is prospected.