title: Mechanisms of ER stress-induced apoptosis in atherosclerosis.
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.
authors.affiliation: Department of Medicine, Columbia University-PH 9-405, 630 W. 168th St., New York, NY 10032, USA. cms2232@columbia.edu
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Scull
authors.forename: Ira
authors.initials: I
authors.lastname: Tabas
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D050197:Atherosclerosis / Q000503:physiopathology*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D004722:Endoribonucleases / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology*; D051742:Transcription Factor CHOP / Q000502:physiology; D056811:Unfolded Protein Response / Q000502:physiology
chemical_list: C497249:DDIT3 protein, human; D008565:Membrane Proteins; D051742:Transcription Factor CHOP; C403982:ERN2 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
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