title: Impact of oxidized low density lipoprotein on vascular cells.
abstract: Oxidized LDL (OxLDL) is a proatherogenic lipoprotein, accumulating in the vascular wall and contributing to the pathogenesis of vascular dysfunction early in the development of atherosclerosis. Enhanced serum levels of OxLDL, as well as antibodies against its epitopes, are predictive for endothelial dysfunction and coronary heart disease. While enhanced oxidative stress is one factor triggering formation of OxLDL, OxLDL itself has been identified as a potent stimulus for vascular oxygen radical formation, causing a vicious circle. OxLDL-induced O(2)(-) formation, largely through activation of NADPH oxidase, but also through uncoupling of endothelial NO-synthase and through direct O(2)(-) release, leads to endothelial dysfunction. Furthermore, OxLDL-induced O(2)(-) formation has a strong impact on tissue remodeling, resulting in either cell growth - proliferation or hyperplasia - or apoptotic cell death. The effect of OxLDL on cell cycle regulation is mediated by activation of the small GTPase RhoA and consequent regulation of p27(KIP1), a key enzyme of the cell cycle. In addition, OxLDL-induced activation of RhoA sensitizes the contractile apparatus of the vessel wall, enhancing the contractile tonus and favoring vasospasm. Thus, through a variety of mechanisms, OxLDL importantly contributes to vascular dysfunction and remodeling.
authors.affiliation: Department of Medicine, Division of Nephrology, Julius-Maximilians-University, Würzburg, Germany. j-c.galle@mail.uni-wuerzburg.de
authors.forename: Jan
authors.initials: J
authors.lastname: Galle
authors.forename: Thomas
authors.initials: T
authors.lastname: Hansen-Hagge
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Stefan
authors.initials: S
authors.lastname: Seibold
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology*; D002453:Cell Cycle / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005609:Free Radicals; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014661:Vasoconstriction
chemical_list: D005609:Free Radicals; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein