ISSN 0371-0874, CN 31-1352/Q

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内皮功能障碍在高同型半胱氨酸致动脉粥样硬化中作用及机制的研究进展

武成艳, 段旭磊, 王立波, 王学惠*

新乡医学院第一附属医院心内科,新乡医学院心脏诊疗中心,新乡 453100

摘要

高同型半胱氨酸血症(hyperhomocysteinemia, HHcy)被认为是心血管疾病的独立危险因素,但其致病的具体分子机制尚未完全明确。内皮功能障碍是动脉粥样硬化的关键始动环节,而这在HHcy所致血管疾病中可普遍被观察到。HHcy促进氧化应激、抑制一氧化氮产生、抑制硫化氢信号通路、促进内皮间充质转化、激活凝血途径,促进蛋白质N-同型半胱氨酸化和细胞低甲基化等都可引起内皮功能的破坏。本文综述了HHcy与内皮功能障碍间的具体联系,并强调了最新证据内皮间充质转化参与调节HHcy致血管毒性,有望为其临床治疗提供新的思路。

关键词: 高同型半胱氨酸血症; 内皮功能障碍; 内皮间充质转化; 动脉粥样硬化

Research progress on the role and mechanism of endothelial dysfunction in hyperhomocysteine-induced atherosclerosis

WU Cheng-Yan, DUAN Xu-Lei, WANG Li-Bo, WANG Xue-Hui*

Department of Cardiology, The First Affiliated Hospital of Xinxiang Medical University; Heart Center of Xinxiang Medical University, Xinxiang 453100, China

Abstract

Hyperhomocysteinemia (HHcy) is considered to be an independent risk factor for cardiovascular diseases, but the molecular mechanisms underlying its pathogenesis are not fully understood. Endothelial dysfunction is a key initiating factor in the pathogenesis of atherosclerosis, which is commonly observed in almost all HHcy-induced vascular diseases. HHcy promotes oxidative stress, inhibits nitric oxide production, suppresses hydrogen sulfide signaling pathway, promotes endothelial mesenchymal transition, activates coagulation pathways, and promotes protein N-homocysteination and cellular hypomethylation, all of which can cause endothelial dysfunction. This article reviews the specific links between HHcy and endothelial dysfunction, and highlights recent evidence that endothelial mesenchymal transition contributes to HHcy-induced vascular damage, with a hope to provide new ideas for the clinical treatment of HHcy-related vascular diseases.

Key words: hyperhomocysteinemia; endothelial dysfunction; endothelial mesenchymal transition; atherosclerosis

收稿日期:  录用日期:

通讯作者:王学惠  E-mail: 121045@xxmu.edu.cn

DOI: 10.13294/j.aps.2023.0063

引用本文:

武成艳, 段旭磊, 王立波, 王学惠. 内皮功能障碍在高同型半胱氨酸致动脉粥样硬化中作用及机制的研究进展[J]. 生理学报 2023; 75 (5): 703-713.

WU Cheng-Yan, DUAN Xu-Lei, WANG Li-Bo, WANG Xue-Hui. Research progress on the role and mechanism of endothelial dysfunction in hyperhomocysteine-induced atherosclerosis. Acta Physiol Sin 2023; 75 (5): 703-713 (in Chinese with English abstract).