Ajoolabady Amir, Wang Shuyi, Kroemer Guido, Klionsky Daniel J, Uversky Vladimir N, Sowers James R, Aslkhodapasandhokmabad Hamid, Bi Yaguang, Ge Junbo, Ren Jun
University of Wyoming College of Health Sciences, Laramie, Wyoming 82071, USA.
School of Medicine Shanghai University, Shanghai 200444, China.
Endocr Rev. 2021 Nov 16;42(6):839-871. doi: 10.1210/endrev/bnab006.
The 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 proinflammatory cytokines may contribute to the onset and progression of cardiometabolic diseases, it is well perceived that ER stress also evokes the onset and development of cardiometabolic diseases, particularly cardiovascular diseases (CVDs), diabetes mellitus, obesity, and chronic kidney disease (CKD). 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 CVDs, diabetes mellitus, obesity, and CKD, hoping to offer novel insights for the management of these cardiometabolic comorbidities through regulation of ER stress.
内质网（ER）容纳线性多肽，并通过内质网驻留伴侣蛋白和酶促进蛋白质的自然折叠。内质网无法排列和构建合适的蛋白质结构会导致内质网腔中错误折叠/未折叠蛋白质的积累，这会扰乱内质网稳态，引发内质网应激。内质网应激的存在会启动细胞保护性未折叠蛋白反应（UPR）以恢复内质网稳态，或引发适应性较差的未折叠蛋白反应以促进细胞死亡。尽管诸如持续性自噬、线粒体自噬失调和促炎细胞因子分泌等多种细胞过程可能导致心脏代谢疾病的发生和进展，但人们普遍认为内质网应激也会引发心脏代谢疾病，特别是心血管疾病（CVD）、糖尿病、肥胖症和慢性肾脏病（CKD）的发生和发展。同时，这些病理状况会进一步加重内质网应激，形成一个恶性循环。在本综述中，我们旨在总结和更新有关心血管疾病、糖尿病、肥胖症和慢性肾脏病内质网应激的现有信息，希望通过调节内质网应激为这些心脏代谢合并症的管理提供新的见解。
