内质网应激与心血管疾病

Endoplasmic reticulum stress and cardiovascular diseases

内质网(endoplasmic reticulum,ER)是细胞内蛋白质折叠、Ca2+储存和脂质生物合成的重要部位。氧化应激、缺血、Ca2+稳态的失衡都可以引起ER内非折叠蛋白的聚集,通过ER内的分子伴侣激活非折叠蛋白反应(unfolded protein response,UPR)可促进细胞的生存,但是过度ER应激(endoplasmic reticulum stress,ERS)可以诱导凋亡信号起始,通过线粒体依赖或者非线粒体依赖途径导致细胞死亡。因此,近年来ER被认为是决定细胞生存与凋亡的重要器官。最近研究提示,ERS在多种心血管疾病的病生理机制中起着重要作用,包括心功能不全及缺血性心脏疾病等。对这些疾病分子机制的进一步认识,将有助于开发新的靶向药物并治疗疾病。本文将对ERS和其与心血管疾病的关系进行综述。

Endoplasmic reticulum （ER） is an and lipid biosynthesis. Various factors can lead organelle involved in protein folding, calcium homeostasis to the accumulation of unfolded proteins including oxidative stress, ischemia and disturbance of calcium homeostasis, which will trigger the unfolded protein response （UPR） by chaperons in the ER to promote cellular survival. However, if stress is severe, ER stress （ERS） also initiates apoptotic signaling to lead to cell death via mitochondria-dependent and -independent apoptotic pathways. Thus, ER is now recognized as a vitally important organelle that can decide cell survival or death. Recent studies have revealed that ERS is related to the pathophysiology of various cardiovascular diseases such as heart failure and ischemic heart disease. A better understanding of molecular mechanisms will provide us with new targets for drug discovery and therapeutic intervention. This article will make an introduction of ERS and its relationship with cardiovascular diseases.