Attenuation of NADPH Oxidase Activation and Glomerular Filtration Barrier Remodeling With Statin Treatment

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Attenuation of NADPH Oxidase Activation and Glomerular Filtration Barrier Remodeling With Statin Treatment

Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/8495

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dc.contributor.author Whaley-Connell, Adam T.
dc.contributor.author Habibi, Javad, 1947-
dc.contributor.author Nistala, Ravi
dc.contributor.author Cooper, Shawna A.
dc.contributor.author Karuparthi, Poorna R.
dc.contributor.author Hayden, Melvin
dc.contributor.author DeMarco, Vincent G.
dc.contributor.author Andresen, Bradley T.
dc.contributor.author Wei, Yongzhong
dc.contributor.author Ferrario, Carlos M.
dc.contributor.author Sowers, James R. (James Russell), 1942-
dc.date.accessioned 2010-09-14T19:28:09Z
dc.date.available 2010-09-14T19:28:09Z
dc.date.issued 2008
dc.identifier.citation Attenuation of NADPH Oxidase Activation and Glomerular Filtration Barrier Remodeling With Statin Treatment. Hypertension, 51, 474-480. en_US
dc.identifier.issn 1524-4563
dc.identifier.uri http://hdl.handle.net/10355/8495
dc.description.abstract Activation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase by angiotensin II is integral to the formation of oxidative stress in the vasculature and the kidney. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibition is associated with reductions of oxidative stress in the vasculature and kidney and associated decreases in albuminuria. Effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibition on oxidative stress in the kidney and filtration barrier integrity are poorly understood. To investigate, we used transgenic TG(mRen2)27(Ren2) rats, which harbor the mouse renin transgene and renin-angiotensin system activation, and an immortalized murine podocyte cell line. We treated young, male Ren2 and Sprague-Dawley rats with rosuvastatin (20 mg/kg IP) or placebo for 21 days. Compared with controls, we observed increases in systolic blood pressure, albuminuria, renal NADPH oxidase activity, and 3-nitrotryosine staining, with reductions in the rosuvastatin-treated Ren2. Structural changes on light and transmission electron microscopy, consistent with periarteriolar fibrosis and podocyte foot-process effacement, were attenuated with statin treatment. Nephrin expression was diminished in the Ren2 kidney and trended to normalize with statin treatment. Angiotensin II- dependent increases in podocyte NADPH oxidase activity and subunit expression (NOX2, NOX4, Rac, and p22phox) and reactive oxygen species generation were decreased after in vitro statin treatment. These data support a role for increased NADPH oxidase activity and subunit expression with resultant reactive oxygen species formation in the kidney and podocyte. Furthermore, statin attenuation of NADPH oxidase activation and reactive oxygen species formation in the kidney/podocyte seems to play roles in the abrogation of oxidative stress-induced filtration barrier injury and consequent albuminuria. en_US
dc.language.iso en_US en_US
dc.publisher American Heart Association, Inc. en_US
dc.relation.ispartof Nephrology publications (MU) en_US
dc.subject progressive glomerular dysfunction en_US
dc.subject RAS en_US
dc.subject endothelial dysfunction en_US
dc.subject.lcsh Statins (Cardiovascular agents) en_US
dc.subject.lcsh Oxidative stress en_US
dc.subject.lcsh Hydroxymethylglutaryl coenzyme A reductases en_US
dc.title Attenuation of NADPH Oxidase Activation and Glomerular Filtration Barrier Remodeling With Statin Treatment en_US
dc.type Article en_US
dc.source.harvested American Heart Association web site en_US
dc.relation.ispartofcommunity University of Missouri-Columbia. School of Medicine. Department of Internal Medicine. Division of Nephrology


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