Title:Endothelial Dysfunction: The Link Between Homocysteine and Hydrogen Sulfide
Volume: 21
Issue: 32
Author(s): Sathnur Pushpakumar, Sourav Kundu and Utpal Sen
Affiliation:
关键词:
功能障碍，内皮细胞层，同型半胱氨酸，硫化氢
摘要: High level of homocysteine (hyperhomocysteinemia, HHcy) is associated with increased risk for vascular disease.
Evidence for this emerges from epidemiological studies which show that HHcy is associated with premature peripheral,
coronary artery and cerebrovascular disease independent of other risk factors. Possible mechanisms by which homocysteine
causes vascular injury include endothelial injury, DNA dysfunction, proliferation of smooth muscle cells, increased
oxidative stress, reduced activity of glutathione peroxidase and promoting inflammation. HHcy has been shown to
cause direct damage to endothelial cells both in vitro and in vivo. Clinically, this manifests as impaired flow-mediated
vasodilation and is mainly due to a reduction in nitric oxide synthesis and bioavailability. The effect of impaired nitric oxide
release can in turn trigger and potentiate atherothrombogenesis and oxidative stress. Endothelial damage is a crucial
aspect of atherosclerosis and precedes overt manifestation of disease. In addition, endothelial dysfunction is also associated
with hypertension, diabetes, ischemia reperfusion injury and neurodegenerative diseases. Homocysteine is a precursor
of hydrogen sulfide (H2S) which is formed by transulfuration process catalyzed by the enzymes, cystathionine β-
synthase and cystathionine γ-lyase. H2S is a gasotransmitter that has emerged recently as a novel mediator in cardiovascular
homeostasis. As a potent vasodilator, it plays several roles which include regulation of vessel diameter, protection of
endothelium from redox stress, ischemia reperfusion injury and chronic inflammation. However, the precise mechanism
by which it mediates these beneficial effects is complex and still remains unclear. Current evidence indicates H2S modulates
cellular functions by a variety of intracellular signaling processes. In this review, we summarize the mechanisms of
HHcy-induced endothelial dysfunction and the metabolism and physiological functions of H2S as a protective agent.
