Targeting hydrogen sulfide as a promising therapeutic strategy for atherosclerosis.

Abstract

Physiological concentrations of nitric oxide (NO) and carbon monoxide (CO) have multiple protective effects in the cardiovascular system. Recent studies have implicated hydrogen sulfide (H2S) as a new member of vasculoprotective gasotransmitter family, behaving similarly to NO and CO. H2S has been demonstrated to inhibit multiple key aspects of atherosclerosis, including atherogenic modification of LDL, monocytes adhesion to the endothelial cells, macrophage-derived foam cell formation and inflammation, smooth muscle cell proliferation, neointimal hyperplasia, vascular calcification, and thrombogenesis. H2S also decreases plasma homocysteine levels in experimental animal models. In the human body, H2S production is predominantly catalyzed by cystathionine-β-synthase (CBS) and cystathionine γ-lyase (CSE). CSE is the primary H2S-producing enzyme in the vasculature. Growing evidence suggests that atherosclerosis is associated with vascular CSE/H2S deficiency and that H2S supplementation by exogenous H2S donors (such as NaHS and GYY4137) attenuates, and H2S synthesis suppression by inhibitors (such as D, L-propargylglycine) aggravates the development of atherosclerotic plaques. However, it remains elusive whether CSE deficiency plays a causative role in atherosclerosis. A recent study (Circulation. 2013; 127: 2523-2534) demonstrates that decreased endogenous H2S production by CSE genetic deletion accelerates atherosclerosis in athero-prone ApoE-/- mice, pinpointing that endogenously produced H2S by CSE activation may be of benefit in the prevention and treatment of atherosclerosis. This study will facilitate the development of H2S-based pharmaceuticals with therapeutic applications in atherosclerosis-related cardiovascular diseases.

• Authors: Suowen Xu, Zhiping Liu, Peiqing Liu
• Journal: International journal of cardiology (Int J Cardiol) Vol. 172 Issue 2 Pg. 313-7 (Mar 15 2014) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 24491853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• GYY 4137
• Morpholines
• Organothiophosphorus Compounds
• Carbon Dioxide
• Nitric Oxide
• Cystathionine gamma-Lyase
• Hydrogen Sulfide

Topics

• Animals
• Atherosclerosis (drug therapy, etiology)
• Carbon Dioxide (metabolism)
• Cystathionine gamma-Lyase (deficiency)
• Humans
• Hydrogen Sulfide (metabolism, pharmacology)
• Mice
• Morpholines (pharmacology)
• Nitric Oxide (metabolism)
• Organothiophosphorus Compounds (pharmacology)
• Oxidative Stress (physiology)
• Signal Transduction (physiology)