title: Pathophysiology of the atherogenic process.
abstract: Atherosclerosis is conceptually defined as the result of a multiplicity of interactive cascades among injurious stimuli and the healing responses of the arterial wall, occurring concurrently within a hyperlipidemic environment. In this discussion, the inflammatory nature of the disease is emphasized. Four aspects of the pathophysiology of atherogenesis are addressed: (1) The role(s) of fluid mechanical or hemodynamic stresses in the focal initiation and/or augmentation of lesions is discussed in terms of the influence of shear stress on endothelial cellular geometry, compliance, membrane anisotropy (r), low-density lipoprotein (LDL)-receptor expression, intracellular potential and replication; (2) mechanisms of blood monocyte recruitment to the arterial intima, including the roles of chemoattractants such as smooth muscle cell-derived chemotactic factor and oxidized LDL; (3) the alternate or "scavenger" receptor pathway of the macrophage and its pivotal roles in foam cell formation and plaque pathogenesis; and (4) the emerging significance of various lipoprotein modifications, and in particular, the oxidative modification of LDL, which facilitates the uptake of the cytotoxic oxidized LDL via the scavenger receptor, thus providing a non-down-regulating mechanism for foam cell formation and plaque development. Evidence indicates that the antioxidant drug probucol prevents the oxidative modification of LDL, thereby retarding atherogenesis independently of cholesterol reduction.
authors.affiliation: Department of Pathology, University of Texas Health Science Center, San Antonio 78284-7750.
authors.forename: C J
authors.initials: CJ
authors.lastname: Schwartz
authors.forename: J L
authors.initials: JL
authors.lastname: Kelley
authors.forename: R M
authors.initials: RM
authors.lastname: Nerem
authors.forename: E A
authors.initials: EA
authors.lastname: Sprague
authors.forename: M M
authors.initials: MM
authors.lastname: Rozek
authors.forename: A J
authors.initials: AJ
authors.lastname: Valente
authors.forename: E H
authors.initials: EH
authors.lastname: Edwards
authors.forename: A R
authors.initials: AR
authors.lastname: Prasad
authors.forename: J J
authors.initials: JJ
authors.lastname: Kerbacher
authors.forename: S A
authors.initials: SA
authors.lastname: Logan
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D005487:Foam Cells / Q000502:physiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D013314:Stress, Mechanical
chemical_list: D008077:Lipoproteins, LDL