Department of Medicine, Columbia University-PH 9-405, 630 W. 168th St., New York, NY 10032, USA.
Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):2792-7. doi: 10.1161/ATVBAHA.111.224881.
Endoplasmic reticulum (ER) stress is triggered by perturbations in ER function such as those caused by protein misfolding or by increases in protein secretion. Eukaryotic cells respond to ER stress by activating 3 ER-resident proteins, activating transcription factor-6, inositol requiring protein-1, and protein kinase RNA-like ER kinase (PERK). These proteins direct signaling pathways that relieve ER stress in a process known as the unfolded protein response (UPR). In pathological settings, however, prolonged UPR activation can promote cell death, and this process has recently emerged as an important concept in atherosclerosis. We review here the evidence for UPR activation and cell death in macrophages, smooth muscle cells, and endothelial cells in the context of advanced atherosclerosis as well as the existing literature regarding mechanisms of UPR-induced cell death. Knowledge in this area may suggest new therapeutic targets relevant to the formation of clinically dangerous atherosclerotic plaques.
内质网（ER）应激是由 ER 功能的紊乱触发的，如蛋白质错误折叠或蛋白质分泌增加等。真核细胞通过激活 3 种 ER 驻留蛋白，即激活转录因子 6、肌醇需求蛋白 1 和蛋白激酶 RNA 样 ER 激酶（PERK）来应对 ER 应激。这些蛋白可指导信号通路，在一个称为未折叠蛋白反应（UPR）的过程中减轻 ER 应激。然而，在病理状态下，长期的 UPR 激活可促进细胞死亡，而这一过程最近已成为动脉粥样硬化中的一个重要概念。我们在此综述了在晚期动脉粥样硬化中巨噬细胞、平滑肌细胞和内皮细胞中 UPR 激活和细胞死亡的证据，以及关于 UPR 诱导细胞死亡的机制的现有文献。该领域的知识可能提示与形成有临床危险的动脉粥样硬化斑块相关的新治疗靶点。
