Attenuation of NADPH oxidase activation and glomerular filtration barrier remodeling with statin treatment
Autor: | Bradley T. Andresen, Nathan Rehmer, Vincent G. DeMarco, Carlos M. Ferrario, Ravi Nistala, Melvin R. Hayden, Yongzhong Wei, Adam Whaley-Connell, Poorna R. Karuparthi, Javad Habibi, James R. Sowers, Shawna A. Cooper |
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Rok vydání: | 2008 |
Předmět: |
Male
medicine.medical_specialty Kidney Cortex Kidney Glomerulus Blood Pressure medicine.disease_cause Article Podocyte Animals Genetically Modified Rats Sprague-Dawley Mice Internal medicine Renin Internal Medicine medicine Albuminuria Animals Rosuvastatin Calcium Cell Line Transformed Kidney Oxidase test Sulfonamides NADPH oxidase biology Podocytes Angiotensin II NOX4 NADPH Oxidases Rats Enzyme Activation Fluorobenzenes Isoenzymes Microscopy Electron Oxidative Stress Endocrinology medicine.anatomical_structure Pyrimidines biology.protein P22phox Hydroxymethylglutaryl-CoA Reductase Inhibitors Reactive Oxygen Species Oxidative stress Biomarkers |
Zdroj: | Hypertension (Dallas, Tex. : 1979). 51(2) |
ISSN: | 1524-4563 |
Popis: | 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 p22 phox ) 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. |
Databáze: | OpenAIRE |
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