Peroxisome Proliferator‐Activated Receptor gamma (PPARgamma) ligand, Rosiglitazone, attenuates vascular oxidative stress in a mouse model of Type 2 Diabetes

Abstract

Purpose The current study was designed to determine if PPARgamma ligands modulate vascular endothelial superoxide generation in vivo through suppressing expression of selected subunits of NADPH oxidase and/or by increasing the expression and activity of Cu/Zn superoxide dismutase. Methods Lean control (db+/db−) and obese, leptin receptor-deficient (db−/db−) mice were treated with either vehicle or rosiglitazone (3 mg/kg/day) by gavage for 7 days. Results Compared to db+/db− mice, obese, db−/db− mice had higher serum glucose, insulin, leptin, triglyceride, and fatty acid levels and lower adiponectin levels. Rosiglitazone had no effect on these metabolic derangements. Aortic superoxide generation measured with ESR spectroscopy was significantly increased in db−/db− mice. Aortic tissue from these mice also demonstrated higher relative mRNA levels of the NADPH oxidase subunits, Nox-1 and Nox-4, as measured by real time PCR analysis and lower mRNA levels of PPARgamma. Rosiglitazone treatment decreased superoxide generation and mRNA levels of Nox homologues in db−/db− mice. Conclusions These data indicate that short-term treatment with the rosiglitazone suppressed vascular NADPH oxidase expression and superoxide production in an animal model of vascular oxidative stress. This work is supported by grants from the Veterans Affairs Research Service