The dichotomous role of nitric oxide in the pathogenesis of accelerated atherosclerosis associated with systemic lupus erythematosus.
Atherosclerosis is an inflammatory disorder, and the inflammation associated with systemic lupus erythematosus (SLE) accelerates the development of atherosclerosis. Nitric oxide (NO) is an important mediator of inflammation including the inflammation associated with atherosclerosis and SLE. Endothelial nitric oxide synthase (NOS3)-mediated constitutive expression of NO promotes endothelial integrity and normal vascular function. In contrast, inducible nitric oxide synthase- (NOS2) mediated expression of NO promotes endothelial dysfunction and atherogenesis. Statins appear to have anti-inflammatory properties and reverse many of the deleterious effects associated with NO metabolism in atherosclerosis. Statins augment NOS3 expression and inhibit the induction of NOS2. Therefore, the balance between normal vascular function and atherogenesis may be mediated by differences in the quantity, location, and timing of NO production within vessel walls.
Levesque
Marc C
MC
From Department of Medicine, Division of Rheumatology, Duke University and Durham VA Medical Centers, Durham, NC, USA. marc.levesque@duke.edu
Weinberg
J Brice
JB
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009569:Nitric Oxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III