Effect of Rosiglitazone on Cardiac Fibroblast Proliferation,Nitric Oxide Production and Connective Tissue Growth Factor Expression Induced by Advanced Glycation End-products

Abstract

This study investigated the effects of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone (RGZ) on cardiac fibroblast proliferation, nitric oxide content and connective tissue growth factor (CTGF) expression following incubation with advanced glycation end-products (AGEs). Cultured neonatal rat cardiac fibroblasts were incubated with various concentrations of AGEs for 48 h. Cells were also incubated with 200 mg/l AGEs plus various concentrations of RGZ. Cardiac fibroblast proliferation and cell cycle status were detected using a 3-(4, 5dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Western blotting was used to measure the expression of CTGF and nitric oxide content was evaluated using a nitrate reductase assay. AGEs significantly accelerated proliferation, increased CTGF expression and decreased nitric oxide production in cardiac fibroblasts. These effects of AGEs were inhibited by RGZ in a dose-dependent manner. Treatment with RGZ could be a valuable therapeutic approach in diabetic patients with myocardial fibrosis.

Keywords

Rosiglitazone Advanced glycation end-products Cardiac fibroblasts Nitric oxide Connective tissue growth factor

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