Cardiovascular Pathogenesis in Hyperhomocysteinemia

同型半胱氨酸血症引起心血管疾病的发病机制

Tao Huang ； Gao-Feng Yuan ； Zhi-Guo Zhang ； Zu-Quan Zou ； Duo Li

《Asia Pacific Journal of Clinical Nutrition》 17卷1期 (2008/03) Pp. 8-16

https://doi.org/10.6133/apjcn.2008.17.1.02

摘要

血浆同型半胱氨酸升高是心血管疾病的独立危害因子。高同型半胱氨酸血症导致多种疾病发生的主要表现有：平滑肌细胞增殖、闭塞性血管病、动脉狭窄、止血能力的改变、胎盘血管病变、自发性早期流产、出生缺陷、认知能力受损和痴呆。该综述总共搜集了1932年到2007年间发表于MEDLINE以及其他杂志上的112篇文章，概述了血浆同型半胱氨酸的升高在心血管病以及其他疾病发生中的作用，同时阐述其在高同型半胱氨酸血症中的病理生理学分子机制。高同型半胱氨酸血症引起心血管疾病的病理生理学是一个复杂的过程，可能的机制是：同型半胱氨酸直接对组织的毒性作用、高S-腺苷同型半胱氨酸、低S-腺苷甲硫氨酸、通过刺激凝血因子和抑制抗凝血因子及血小板活性而引起的血栓形成，继而引起氧化应急、平滑肌细胞增殖、活性氧系列的形成、低甲基化、非折叠蛋白反应、细胞外基质改变。同型半胱氨酸增加心血管疾病危险的机制在某些方面仍然不是很清楚，有待更多的研究来解开这个谜底。

關鍵字

同型半胱氨酸 ； 平滑肌细胞 ； 氧化应急 ； 致畸作用 ； 促炎症反应

並列摘要

Increased plasma homocysteine (Hcy) is a significant and independent risk factor for cardiovascular disease. It can cause multi-disease manifestations such as smooth muscle proliferation, premature occlusive vascular disease, progressive arterial stenosis, haemostatic changes, placental vasculopathy, spontaneous early abortion, birth defects, impaired cognitive function and dementia. This review paper summarizes the role of elevated Hcy levels in cardiovascular and other diseases and the molecular mechanisms and pathophysiology involved in the deleterious manifestations of hyperhomocysteinemia. We have collected data from MEDLINE, Current Contents and scientific journals, which included 112 publications from 1932 to 2007. Cardiovascular pathophysiology in hyperhomocysteinemia is a complicated process, possibly due to direct toxicity of Hcy on tissues, low S-adenosylmethionine, high S-adenosylhomocysteine or thrombotic events triggered by stimulation of procoagulant factors and suppression of anticoagulant factors and platelet activation, thereby enhancing oxidative stress, smooth muscle cell proliferation, formation of reactive oxygen species, hypomethylation, induction of unfolded protein responses and extracellular matrix modification. The mechanisms involved in the increased risk of cardiovascular disease still remains a mystery in many respects, and more studies are needed to elucidate this association.

並列關鍵字

Homocysteine ； smooth muscle cell ； oxidizing stress ； teratogenic action ； proinflammatory