Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Health Science Center, Beijing, China.
Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Br J Pharmacol. 2018 Apr;175(8):1173-1189. doi: 10.1111/bph.13988. Epub 2017 Sep 22.
Homocysteine is a sulphur-containing non-proteinogenic amino acid. Hyperhomocysteinaemia (HHcy), the pathogenic elevation of plasma homocysteine as a result of an imbalance of its metabolism, is an independent risk factor for various vascular diseases, such as atherosclerosis, hypertension, vascular calcification and aneurysm. Treatments aimed at lowering plasma homocysteine via dietary supplementation with folic acids and vitamin B are more effective in preventing vascular disease where the population has a normally low folate consumption than in areas with higher dietary folate. To date, the mechanisms of HHcy-induced vascular injury are not fully understood. HHcy increases oxidative stress and its downstream signalling pathways, resulting in vascular inflammation. HHcy also causes vascular injury via endoplasmic reticulum stress. Moreover, HHcy up-regulates pathogenic genes and down-regulates protective genes via DNA demethylation and methylation respectively. Homocysteinylation of proteins induced by homocysteine also contributes to vascular injury by modulating intracellular redox state and altering protein function. Furthermore, HHcy-induced vascular injury leads to neuronal damage and disease. Also, an HHcy-activated sympathetic system and HHcy-injured adipose tissue also cause vascular injury, thus demonstrating the interactions between the organs injured by HHcy. Here, we have summarized the recent developments in the mechanisms of HHcy-induced vascular injury, which are further considered as potential therapeutic targets in this condition.
This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.
同型半胱氨酸是一种含硫的非蛋白氨基酸。高同型半胱氨酸血症（HHcy）是由于其代谢失衡导致血浆同型半胱氨酸升高的致病因素，是各种血管疾病的独立危险因素，如动脉粥样硬化、高血压、血管钙化和动脉瘤。通过饮食补充叶酸和维生素 B 来降低血浆同型半胱氨酸的治疗方法在叶酸消耗正常的人群中预防血管疾病比在叶酸饮食较高的地区更有效。迄今为止，HHcy 诱导血管损伤的机制尚未完全阐明。HHcy 增加氧化应激及其下游信号通路，导致血管炎症。HHcy 还通过内质网应激引起血管损伤。此外，HHcy 通过 DNA 去甲基化和甲基化分别上调致病基因和下调保护基因。同型半胱氨酸诱导的蛋白质同型半胱氨酸化也通过调节细胞内氧化还原状态和改变蛋白质功能导致血管损伤。此外，HHcy 诱导的血管损伤导致神经元损伤和疾病。HHcy 激活的交感神经系统和 HHcy 损伤的脂肪组织也会导致血管损伤，从而表明 HHcy 损伤的器官之间存在相互作用。在这里，我们总结了 HHcy 诱导血管损伤机制的最新进展，这些进展进一步被认为是该疾病的潜在治疗靶点。
本文是心血管疾病小分子聚焦专题的一部分。要查看本部分中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.
