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Review
. 2011 Dec;31(12):2792-7.
doi: 10.1161/ATVBAHA.111.224881.

Mechanisms of ER stress-induced apoptosis in atherosclerosis

Christopher M Scull  1 , Ira Tabas
Affiliations
Review

Mechanisms of ER stress-induced apoptosis in atherosclerosis

Christopher M Scull et al. Arterioscler Thromb Vasc Biol. 2011 Dec.

Abstract

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.

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Figures

Figure 1
Figure 1. Pro-apoptotic signaling mediated by ER stress
During prolonged activation of the UPR, activation of ER stress sensors can lead to both mitochondria-independent and -dependent apoptosis. Activation of PERK and ATF6 leads to induction of CHOP, which in turn can cause changes in BCL-2 family proteins as well as activate calcium signaling pathways to cause cell death. Activation of IRE1 can also lead to calcium release from the ER, in addition to inducing apoptosis through RIDD or a BCL-2-mediated and mitochondria-dependent fashion.
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References

    1. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007;8:519–529. - PubMed
    1. Sriburi R, Jackowski S, Mori K, Brewer JW. XBP1: a link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum. J Cell Biol. 2004;167:35–41. - PMC - PubMed
    1. Tabas I, Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol. 2011;13:184–190. - PMC - PubMed
    1. Myoishi M, Hao H, Minamino T, Watanabe K, Nishihira K, Hatakeyama K, Asada Y, Okada K, Ishibashi-Ueda H, Gabbiani G, Bochaton-Piallat ML, Mochizuki N, Kitakaze M. Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome. Circulation. 2007;116:1226–1233. - PubMed
    1. Tabas I. The role of endoplasmic reticulum stress in the progression of atherosclerosis. Circ Res. 2010;107:839–850. - PMC - PubMed

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