title: Endothelial cell apoptosis: biochemical characteristics and potential implications for atherosclerosis.
abstract: The high turnover of endothelial cells (EC) in atherosclerosis suggests that an increase in the frequency of both cell proliferation and cell death is important in the pathogenesis of this common disorder. Further, increased apoptosis of EC, smooth muscle cells (SMC) and immune cells has been observed in atheromatous plaques. Many pro-atherogenic factors, including oxidized low-density lipoproteins, angiotensin II and oxidative stress, can induce EC apoptosis. Such damage to the endothelium may be an initiating event in atherogenesis since EC apoptosis may compromise vasoregulation, increase SMC proliferation, SMC migration and blood coagulation. In addition, EC overlying vascular lesions have been shown to increase their expression of pro-apoptotic proteins, such as Fas and Bax, while decreasing levels of anti-apoptotic factors. Therefore, understanding EC apoptotic pathways that are altered in atherosclerosis may enable a greater understanding of disease pathogenesis and foster the development of new therapies. The present discussion outlines the biochemical characteristics of EC apoptosis and the role that altered regulation of apoptosis plays in vasculopathy.
authors.affiliation: UBC McDonald Research Laboratories/The iCAPTUR4E Centre, Department of Pathology and Laboratory Medicine, St. Paul's Hospital/Providence Health Care-University of British Columbia, Vancouver, BC, Canada.
authors.forename: J C
authors.initials: JC
authors.lastname: Choy
authors.forename: D J
authors.initials: DJ
authors.lastname: Granville
authors.forename: D W
authors.initials: DW
authors.lastname: Hunt
authors.forename: B M
authors.initials: BM
authors.lastname: McManus
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D017209:Apoptosis; D001161:Arteriosclerosis / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D053222:Fas Ligand Protein; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008077:Lipoproteins, LDL; D008222:Lymphokines; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C099252:oxidized low density lipoprotein; D000804:Angiotensin II; D009569:Nitric Oxide; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium