The molecular basis of homocysteine thiolactone-mediated vascular disease
The molecular basis of homocysteine thiolactone-mediated vascular disease
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DOI：
10.1515/cclm.2007.338
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发表时间：
2007-01-01
影响因子：
6.8
通讯作者：
Jakubowski, Hieronim
中科院分区：
文献类型：
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作者：
Jakubowski, Hieronim
越来越多的证据表明，同型半胱氨酸（Hcy）的代谢物硫酯Hcy-硫内酯在动脉粥样硬化和血栓形成中起重要作用。hcy -硫内酯水平在高同型半胱氨酸血症的人和小鼠中升高。hcy -硫代内酯的硫酯化学是其与蛋白质赖氨酸残基形成异粒子键的能力的基础，这损害或改变了蛋白质的功能。人血液中hcy -硫内酯修饰的蛋白靶点包括纤维蛋白原、低密度脂蛋白和高密度脂蛋白。蛋白n -同型半胱氨酸化导致病理生理反应，包括由n - hcy纤维蛋白原引起的血栓形成易感性增加，以及由n - hcy蛋白引起的自身免疫反应。在高同型半胱氨酸血症中，这些反应多年的慢性激活可能导致血管疾病。本文综述了最近的证据支持假说，即Hcy-硫内酯有助于Hcy对血管系统的病理生理作用。
Accumulating evidence suggests that a metabolite of homocysteine (Hcy), the thioester Hcy-thiolactone, plays an important role in atherogenesis and thrombosis. Hcy-thiolactone levels are elevated in hyper-homocysteinemic humans and mice. The thioester chemistry of Hcy-thiolactone underlies its ability to form isopepticle bonds with protein lysine residues, which impairs or alters the protein's function. Protein targets for the modification by Hcy-thiolactone in human blood include fibrinogen, low-density lipoprotein, and high-density lipoprotein. Protein N-homocysteinylation leads to pathophysiological responses, including increased susceptibility to thrombogenesis caused by N-Hcy-fibrinogen, and an autoimmune response elicited by N-Hcy-proteins. Chronic activation of these responses in hyperhomocysteinemia over many years could lead to vascular disease. This article reviews recent evidence supporting the hypothesis that Hcy-thiolactone contributes to pathophysiological effects of Hcy on the vascular system.