NADPH oxidase in endothelial cells: impact on atherosclerosis.
An elevated vascular superoxide anion formation has been implicated in the initiation and progression of hypertension and atherosclerosis. In this review, we would like to discuss the generation of superoxide anions by an NADPH oxidase complex in vascular cells. Special focus is on the induction of endothelial NADPH oxidase by proatherosclerotic stimuli. We propose a proatherosclerotic vicious cycle of increased NADPH oxidase-dependent superoxide anion formation, augmented generation and uptake of oxidatively modified low-density lipoprotein, and further potentiation of oxidative stress by oxidized low-density lipoprotein itself, angiotensin II, and endothelin-1 in endothelial cells. Furthermore, novel homologues of NADPH oxidase subunit gp91(phox) are summarized. Future directions of research for a better understanding of the role of NADPH oxidase in the pathogenesis of atherosclerosis and clinical implications are discussed.
Rueckschloss
Uwe
U
Institute of Pathophysiology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Magdeburger Strasse 18, D-06097 Halle, Germany.
Duerrschmidt
Nicole
N
Morawietz
Henning
H
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology*; D002462:Cell Membrane / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology*; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D020033:Protein Isoforms; D013329:Structure-Activity Relationship
D019332:Endothelin-1; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; C099252:oxidized low density lipoprotein; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D010100:Oxygen