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Acta Pharmacologica Sinica (2016) 37: 425443 2016 CPS and SIMM All rights reserved 1671-4083/16 www.nature.com/aps
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Review
Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases
Mei-qing LIU#, Zhe CHEN#, Lin-xi CHEN*
Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China
Endoplasmic reticulum is a principal organelle responsible for folding, post-translational modications and transport of secretory, luminal and membrane proteins, thus palys an important rale in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is a condition that is accelerated by accumulation of unfolded/misfolded proteins after endoplasmic reticulum environment disturbance, triggered by a variety of physiological and pathological factors, such as nutrient deprivation, altered glycosylation, calcium depletion, oxidative stress, DNA damage and energy disturbance, etc. ERS may initiate the unfolded protein response (UPR) to restore cellular homeostasis or lead to apoptosis. Numerous studies have claried the link between ERS and cardiovascular diseases. This review focuses on ERS-associated molecular mechanisms that participate in physiological and pathophysiological processes of heart and blood vessels. In addition, a number of drugs that regulate ERS was introduced, which may be used to treat cardiovascular diseases. This review may open new avenues for studying the pathogenesis of cardiovascular diseases and discovering novel drugs targeting ERS.
Keywords: endoplasmic reticulum stress; unfolded protein response; ischemic cardiomyopathy; atherosclerosis; hypertension; cardiac hypertrophy; heart failure
Acta Pharmacologica Sinica (2016) 37: 425443; doi: 10.1038/aps.2015.145; published online 1 Feb 2016
Introduction
The endoplasmic reticulum (ER) is a principal organelle responsible for folding, post-translational modications, and transport of secretory, luminal and membrane proteins and is capable of maintaining cellular homeostasis. Newly synthesized and secretory membrane proteins transfer into the endoplasmic reticulum for modification. The modification processes include protein folding, glycosylation and disulde bond formation[1]. The ER quality control system (ERQC) is a system that prevents protein aggregation by promoting correct folding or selective degradation of the improperly folded poly-peptide[2]. This process is regulated by molecular chaperones, foldases, and lectins that maintain the ERQC. ER associates with many processes including apoptosis and autophagy[3].
Endoplasmic reticulum stress (ERS) is a condition that is accelerated by the accumulation of unfolded/misfolded proteins after a disturbance in the ERQC owing to a variety of physiological and pathological phenomena[4]. Nutrient deprivation, altered glycosylation, calcium depletion, oxida-
tive stress, DNA...