Abstract

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.

中文翻译：

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心脏代谢疾病中的内质网应激：从分子机制到治疗

 抽象的

内质网 (ER) 含有线性多肽，并通过 ER 内的分子伴侣和酶促进蛋白质的自然折叠。内质网未能排列和组成适当的蛋白质结构会导致错误折叠/未折叠蛋白质在内质网管腔中积累，从而扰乱内质网稳态，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，或引发相当不适应的未折叠蛋白反应以促进细胞死亡。尽管一系列广泛的细胞过程，如持续自噬、失调的线粒体自噬和促炎细胞因子的分泌可能有助于心脏代谢疾病的发生和进展，但众所周知，内质网应激也会诱发心脏代谢疾病，特别是心血管疾病的发生和发展。疾病（CVD）、糖尿病、肥胖和慢性肾病（CKD）。同时，这些病理状况进一步加剧内质网应激，形成相当恶性的循环。在这篇综述中，我们的目的是总结和更新有关 CVD、糖尿病、肥胖和 CKD 中 ER 应激的现有信息，希望通过调节 ER 应激为这些心脏代谢合并症的管理提供新的见解。