Pioglitazone Alleviates Cardiac Fibrosis and Inhibits Endothelial to Mesenchymal Transition Induced by Pressure Overload

Abstract

Background/aims: Cardiac fibrosis, characterized by an unbalanced production and degradation of extracellular matrix components, is a common pathophysiology of multiple cardiovascular diseases. Recent studies suggested that endothelial to mesenchymal transition (EndMT) could be a source of activated fibroblasts and contribute to cardiac fibrosis. Here, the role of pioglitazone (PIO) in cardiac fibrosis and EndMT was elaborated.

Methods: Male C57BL/6 mice were subjected to aortic banding (AB), which was used to construct a model of pressure overload-induced cardiac hypertrophy. PIO and GW9662 was given for 4 weeks to detect the effects of PIO on EndMT.

Results: Our results showed PIO treatment attenuated cardiac hypertrophy, dysfunction and fibrosis response to pressure overload. Mechanistically, PIO suppressed the TGF-β/Smad signaling pathway activated by 4-week AB surgery. Moreover, PIO dramatically inhibited EndMT in vivo and in vitro stimulated by pressure overload or TGF-β. A selective antagonist of PPAR-γ, GW9662, neutralized the anti-fibrotic effect and abolished the inhibitory effect of EndMT during the treatment of PIO.

Conclusion: Our data implied that PIO exerts an alleviative effect on cardiac fibrosis via inhibition of the TGF-β/Smad signaling pathway and EndMT by activating PPAR-γ.

Keywords: Cardiac fibrosis; EndMT; Pioglitazone; Ppar-γ.