Abstract: Objective To investigate whether peroxisome proliferator-activated receptor-γ (PPAR-γ) activation inhibits cardiac fibrosis through the angiotensin II (Ang II)-Ets-1 pathway. Methods Primary cultured cardiac fibroblasts (CFs) of rats were divided into these groups: control, Ang II, Ang II+ rosiglitazone, Ang II+ other PPAR-γ ligands, Ang II+ PPAR-γ antagonists. The change in expression of Ets-1, connective tissue growth factor (CTGF), transforming growth factor (TGF)-β1 and Smad2/3 were assessed by using real-time RT-PCR and western blotting. Results In growth-arrested CFs, Ang II induced the expression of Ets-1 mRNA and protein（P < 0.05）, up-regulated expression of Ets-1 down stream target CTGF (P < 0.05), enhanced the expression of TGF-β1 and the expression and phosphorylation of Smad2/3 (P < 0.05). PPAR-γ ligands rosiglitazone and 15d-PGJ2 attenuated the expression of Ang II-induced Ets-1 mRNA and protein (P < 0.05), decreased the induction of CTGF by Ang II (P < 0.05), inhibited in part the expression of TGF-β1 and the expression and phosphorylation of Smad2/3 induced by Ang II (P < 0.05). These suppressive effects on Ets-1 and CTGF were attenuated by PPAR-γ antagonists GW9662 and BADGE (P < 0.05). Conclusions Activation of PPAR-γ inhibits Ang II-induced Ets-1 expression via the TGF-β1/Smad2/3 signaling pathway.

Key words: PPAR-γ, angiotensin II, fibrosis, Ets-1, CTGF