The role of oxidative stress and NADPH oxidase in the pathogenesis of atherosclerosis.
Reactive oxygen species (ROS) play a key role in the pathogenesis of atherosclerosis. The main mechanisms which are involved are low-density lipoprotein oxidative modification, inactivation of nitric oxide and modulation of redox-sensitive signaling pathways. ROS contribute to several aspects of atherosclerosis including endothelial cell dysfunction, monocyte/macrophage recruitment and activation, stimulation of inflammation, and inducing smooth muscle cell migration and proliferation. NADPH oxidase is the main source of ROS in the vasculature. This enzyme consists of a membrane-bound heterodimer of gp91phox and p22phox, cytosolic regulatory subunits p47phox, p67phox and p40phox, and small GTP-binding proteins rac1 and rac 2. Seven distinct isoforms of this enzyme have been identified, of which four (NOX1, 2, 4 and 5) may have cardiovascular function. In this paper, we review the current state of knowledge concerning the role of oxidative stress and NOX enzymes in pathogenesis of atherosclerosis. Moreover, we analyze the experimental studies that explore the relationship between the NOX family and atherosclerosis.
Katedra Biochemii i Chemii Klinicznej Warszawskiego Uniwersytetu Medycznego.
Dorota
D
Bryk
Katedra Biochemii i Chemii Klinicznej Warszawskiego Uniwersytetu Medycznego.
Wioletta
W
Olejarz
Katedra Biochemii i Chemii Klinicznej Warszawskiego Uniwersytetu Medycznego.
Danuta
D
Zapolska-Downar
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D020033:Protein Isoforms / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D008077:Lipoproteins, LDL; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D019255:NADPH Oxidases