title: Pathogenesis of atherosclerosis.
abstract: The earliest lesion in the development of an atherosclerotic plaque is the fatty streak. This chronic inflammatory reaction results from a sequence of events that begins with the trapping of low density lipoprotein (LDL) in the subendothelial space of the artery wall. The trapped LDL is seeded with oxidative species released by the overlying endothelium, and lipid oxidation is initiated within the LDL particle. Some of the lipids that result lead to the activation of NFkB-like transcription factors that cause the expression of genes whose protein products mediate monocyte binding, monocyte chemotaxis into the subendothelial space, and conversion into macrophages. At least 1 major gene modulates the oxidation of LDL lipids and/or the biologic response to these lipids. The inverse relation between high density lipoprotein (HDL) and atherosclerotic events may in part be due to enzymes associated with HDL that destroy the biologically active lipids generated in LDL.
authors.affiliation: Department of Medicine, University of California, Los Angeles, USA.
authors.forename: M
authors.initials: M
authors.lastname: Navab
authors.forename: A M
authors.initials: AM
authors.lastname: Fogelman
authors.forename: J A
authors.initials: JA
authors.lastname: Berliner
authors.forename: M C
authors.initials: MC
authors.lastname: Territo
authors.forename: L L
authors.initials: LL
authors.lastname: Demer
authors.forename: J S
authors.initials: JS
authors.lastname: Frank
authors.forename: A D
authors.initials: AD
authors.lastname: Watson
authors.forename: P A
authors.initials: PA
authors.lastname: Edwards
authors.forename: A J
authors.initials: AJ
authors.lastname: Lusis
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D010741:Phospholipases A / Q000502:physiology
chemical_list: D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase