Effect of rosiglitazone on cardiac fibroblast proliferation, nitric oxide production and connective tissue growth factor expression induced by advanced glycation end-products.
This study investigated the effects of the peroxisome proliferator-activated receptor-gamma 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-(4,5-dimethylthiazol-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.
Li
J
J
Department of Geriatrics, Zhongda Hospital of Southeast University, Nanjing 21009, Jiangsu Province, People's Republic of China.
Liu
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NF
Wei
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D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D047495:PPAR gamma / Q000819:agonists*; D051381:Rats; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
C526317:CCN2 protein, human; C526316:CCN2 protein, rat; D017127:Glycation End Products, Advanced; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D055513:Connective Tissue Growth Factor; D009569:Nitric Oxide