ER stress in Cardiometabolic Diseases: from Molecular Mechanisms to Therapeutics

Endocr Rev. 2021 Mar 8:bnab006. doi: 10.1210/endrev/bnab006. Online ahead of print.ABSTRACTThe endoplasmic reticulum (ER) hosts linear polypeptides and fosters natural folding of proteins through ER-residing chaperones and enzymes. Failure of the ER to align and compose proper protein architecture leads to accumulation of misfolded/unfolded proteins in the ER lumen, which disturbs ER homeostasis to provoke ER stress. Presence of ER stress initiates the cytoprotective unfolded protein response (UPR) to restore ER homeostasis or instigates a rather maladaptive UPR to promote cell death. Although a wide array of cellular processes such as persistent autophagy, dysregulated mitophagy, and secretion of pro-inflammatory cytokines may contribute to the onset and progression of cardiometabolic diseases, it is well perceived that ER stress also evokes onset and development of cardiometabolic diseases, particularly, cardiovascular diseases, diabetes mellitus, obesity, and chronic kidney disease. Meanwhile, these pathological conditions further aggravate ER stress, creating a rather vicious cycle. Here in this review, we aimed at summarizing and updating the available information on ER stress in cardiovascular diseases, diabetes mellitus, obesity, and chronic kidney disease, hoping to offer novel insights for the management of these cardiometabolic comorbidities through regulation of ER stress.PMID:33693711 | DOI:10.1210/endrev/bnab006
Source: Endocrine Reviews - Category: Endocrinology Authors: Source Type: research