摘要
高水平的同型半胱氨酸(高同型半胱氨酸血症,HHcy)与血管疾病的风险增加有关。流行病学研究的证据表明HHcy与早期的外围冠状动脉脑血管疾病的发展及其他危险因素有关。可能的机制包括同型半胱氨酸引起血管损伤包括内皮损伤、DNA功能障碍、平滑肌细胞增殖、氧化应激的增强、减少谷胱甘肽过氧化物酶的活性及促进炎症。HHcy已被证明会在细胞内和细胞外直接损伤内皮细胞。临床上,这表现为血流介导的血管受损,主要是因为一氧化氮合成和生物利用度的减少。受损的一氧化氮的释放造成的影响可以反过来促进和加强动脉粥样硬化-血栓形成和氧化应激。内皮损伤是动脉粥样硬化和先于疾病表现的一个至关重要的方面。此外,内皮功能障碍也与高血压、糖尿病、再灌注损伤和神经退行性疾病有关。同型半胱氨酸是硫化氢(H2S)的一个前体,H2S是在转硫化过程中由酶,胱硫醚β-合酶和胱硫醚γ-裂解酶催化行成的。H2S是一种气体递质,是最近出现的一种在心血管体内平衡中起作用的新颖的调节器。作为一种有效的血管舒张药,它发挥着不同的作用,包括调节血管直径,保护内皮免受氧化还原应激,再灌注损伤和慢性炎症。然而,由它所介导的这些有利影响的明确机制是复杂的,且仍然是不清楚的。目前证据表明H2S通过一系列的细胞内的信号处理来调节细胞功能。在这篇综述中,我们总结了HHcy诱导的内皮功能障碍的机制和H2S作为一种防护剂的代谢和生理功能。
关键词: 功能障碍,内皮细胞层,同型半胱氨酸,硫化氢
Current Medicinal Chemistry
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.
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Cite this article as:
Pushpakumar Sathnur, Kundu Sourav and Sen Utpal, Endothelial Dysfunction: The Link Between Homocysteine and Hydrogen Sulfide, Current Medicinal Chemistry 2014; 21 (32) . https://dx.doi.org/10.2174/0929867321666140706142335
DOI https://dx.doi.org/10.2174/0929867321666140706142335 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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