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内质网应激与心血管疾病关系的研究进展

吉登仁¹, 齐永芬^1,2,3,*

¹北京大学基础医学院生物活性小分子，北京 100083研究室；²北京大学医学部分子心血管学教育部重点实验室，北京 100083；³北京大学基础医学院病原生物学系，北京 100083

摘要

内质网是蛋白质折叠、转录后修饰和转运的重要细胞器，对维持细胞稳态具有重要作用。多种内外环境刺激能够引 起内质网内错误折叠或未折叠蛋白的积累，即形成内质网应激。内质网应激激活未折叠蛋白反应(unfolded protein response, UPR)，进而启动一系列下游信号以维持内质网稳态。但持续或过度的内质网应激激活的UPR最终导致细胞凋亡和疾病。近 年来，大量研究证据表明，内质网应激参与多种心血管疾病(cardiovascular disease, CVD)的发生和发展，包括缺血性心脏 病、糖尿病性心肌病、心力衰竭、动脉粥样硬化、血管钙化、高血压和主动脉瘤等，是治疗多种CVD的重要靶点。本文就内质网应激激活UPR在多种常见CVD中的调控机制以及内质网应激与CVD关系的研究进展作一简要综述。

关键词： 内质网应激; 未折叠蛋白反应; 心血管疾病

分类号：R363.1

New research advances in relationship of endoplasmic reticulum stress and cardiovascular diseases

JI Deng-Ren¹, QI Yong-Fen^1,2,3,*

¹Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, Peking University, Beijing 100083, China；²Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Peking University, Beijing 100083, China；³3Department of Pathogen Biology, School of Basic Medical Sciences, Peking University, Beijing 100083, China

Abstract

Endoplasmic reticulum (ER) is an important organelle for protein folding, post-transcriptional modification and transport, which plays an important role in maintaining cell homeostasis. A variety of internal and external environmental stimuli can cause the accumulation of misfolded or unfolded proteins in the endoplasmic reticulum, and then result in ER stress. ER stress activates the unfolded protein response (UPR) and initiates a cluster of downstream signals to maintain ER homeostasis. However, severe and persistent ER stress activates UPR, which eventually leads to apoptosis and diseases. In recent years, a lot of researches suggest that ER stress plays an important role in the pathogenesis of various cardiovascular diseases (CVD), including ischemic heart disease, diabetic cardiomyopathy, heart failure, atherosclerosis and vascular calcification, high blood pressure and aortic aneurysm. ER stress might be one of the important targets for treatment of multiple CVD. Herein, the regulation mechanism of ER stress by activating UPR pathways in various common CVD and the new research advances in relationship of ER stress and CVD are briefly reviewed.

Key words: endoplasmic reticulum stress; unfolded protein response; cardiovascular disease

收稿日期：2019-08-28　　录用日期：2020-02-27

通讯作者：齐永芬　　E-mail: yongfenqi@163.com

DOI: 10.13294/j.aps.2020.0015

引用本文：

吉登仁, 齐永芬. 内质网应激与心血管疾病关系的研究进展[J]. 生理学报 2020; 72 (2): 190-204.

JI Deng-Ren, QI Yong-Fen. New research advances in relationship of endoplasmic reticulum stress and cardiovascular diseases. Acta Physiol Sin 2020; 72 (2): 190-204 (in Chinese with English abstract).