Transmission of oxLDL-derived lipid peroxide radicals into membranes of vascular cells is the main inducer of oxLDL-mediated oxidative stress.
Oxidatively modified LDL is generally accepted to be an important elicitor of pro-mitotic, pro-inflammatory, and atherogenic effects in vascular cells. The uptake of oxLDL and concomitant activation of the O(2)*-producing NAD(P)H oxidase and/or oxLDL as a self-contained emitter of O(2)* are believed to trigger these malfunctions. The following observations allowed reinvestigating the mode of oxLDL-induced stress: (1) we observed that artery smooth muscle primary cells internalize fluorescently labelled oxidized or acetylated LDL considerably less efficient than endothelial cells. (2) Both types of cells, however, displayed an oxLDL concentration dependent level of oxidative stress as monitored by the oxidation of carboxy-H2DCFDA to fluorescent carboxy-DCF. A dose dependent decrease of dihydroethidine oxidation to oxyethidine implied an oxLDL-induced depletion of the cellular energy pool. The release of O(2)* by exogenous oxLDL, as postulated above, did not sufficiently explain intracellular stress because the fluorescence was only marginally blocked by antioxidative enzymes (SOD, catalase) or substances (L-NAME, DMSO, DMHP, DMTU). We were able to reveal a third mode of oxLDL-induced stress by showing with the help of a fluorescent, oxidizable lipid analogue (BODIPY 581/591 C(11)) that oxLDL-derived lipid peroxides and radicals migrate into cellular membranes giving rise to a chronic inoculation of the vascular cells with oxidative chain reactions. The novel data may help to design adequate therapeutic strategies against oxLDL-induced cardiovascular diseases.
Hansen-Hagge
Thomas E
TE
Department of Medicine, Division of Nephrology, University of Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. hansen@imm-mainz.de
Baumeister
Elke
E
Bauer
Tanja
T
Schmiedeke
Daniel
D
Renné
Thomas
T
Wanner
Christoph
C
Galle
Jan
J
D002462:Cell Membrane / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008054:Lipid Peroxides / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D018384:Oxidative Stress / Q000276:immunology / Q000502:physiology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein