Effects of PPAR-γ activation on angiotensin II-induced extra cellular matrix production and CTGF expression in VSMCs

Objective: To observe the effects of PPAR-γ activation on angiotensin (Ang) II-induced extra cellular matrix (ECM) production and connective tissue growth factor (CTGF) expression in vitro in rat vascular smooth muscle cells (VSMCs). Methods Cultured rat VSMCs were pretreated with PPAR-γ activator rosiglitazone or/and PPAR-γ antagonist GW9662 or BADGE before treated with Ang II for 24 h. The content of hydroxyproline in the cell culture medium was measured by colorimetric assay. Real-time RT-PCR was used to detect collagen III (Col III), fibronectin (FN) and CTGF expression. Protein expressions of CTGF and PPAR-γ were measured by Western blotting. ELISA-based DNA-binding was used to detect PPAR-γ activation. Results: Ang II treatment up-regulated PPAR-γ expression but significantly decreased its activity when compared with control group. Pretreatment of cells with rosiglitazone significantly increased PPAR-γ expression and activation in Ang II-stimulated VSMCs. Rosiglitazone decreased hydroxyproline level in cell culture medium, down-regulated Col III, FN and CTGF expressions in VSMCs. Other PPAR-γ activators had the same effect as rosiglitazone, but PPAR-γ antagonist partly reduced this effect. Conclusion: PPAR-γ activation may inhibit CTGF expression and ECM production in VSMCs. PPAR-γ might act as a therapeutic target for vascular fibrosis.