Cell signaling by reactive nitrogen and oxygen species in atherosclerosis.
The production of reactive oxygen and nitrogen species has been implicated in atherosclerosis principally as means of damaging low-density lipoprotein that in turn initiates the accumulation of cholesterol in macrophages. The diversity of novel oxidative modifications to lipids and proteins recently identified in atherosclerotic lesions has revealed surprising complexity in the mechanisms of oxidative damage and their potential role in atherosclerosis. Oxidative or nitrosative stress does not completely consume intracellular antioxidants leading to cell death as previously thought. Rather, oxidative and nitrosative stress have a more subtle impact on the atherogenic process by modulating intracellular signaling pathways in vascular tissues to affect inflammatory cell adhesion, migration, proliferation, and differentiation. Furthermore, cellular responses can affect the production of nitric oxide, which in turn can strongly influence the nature of oxidative modifications occurring in atherosclerosis. The dynamic interactions between endogenous low concentrations of oxidants or reactive nitrogen species with intracellular signaling pathways may have a general role in processes affecting wound healing to apoptosis, which can provide novel insights into the pathogenesis of atherosclerosis.
Patel
R P
RP
Center for Free Radical Biology, University of Alabama, Birmingham, AL 35294-0019, USA.
Moellering
D
D
Murphy-Ullrich
J
J
Jo
H
H
Beckman
J S
JS
Darley-Usmar
V M
VM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D002450:Cell Communication; D006152:Cyclic GMP / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D013481:Superoxides; D009569:Nitric Oxide; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase; D006162:Guanylate Cyclase; D006152:Cyclic GMP