Key result
Pioglitazone attenuated cardiac hypertrophy, dysfunction, and fibrosis in response to pressure overload by suppressing the TGF-β/Smad signaling pathway and inhibiting EndMT via PPAR-γ activation.
Why the study?
Does pioglitazone alleviate cardiac fibrosis and inhibit endothelial to mesenchymal transition in a mouse model of pressure overload-induced cardiac hypertrophy?
Does pioglitazone alleviate cardiac fibrosis and inhibit endothelial to mesenchymal transition in a mouse model of pressure overload-induced cardiac hypertrophy?
Pioglitazone alleviates pressure overload-induced cardiac fibrosis and hypertrophy in mice by inhibiting endothelial to mesenchymal transition via the PPAR-γ and TGF-β/Smad pathways.
May support PPAR-γ agonism as antifibrotic strategy in pressure overload; leaves open human translation and trials.
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.
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Wei et al. (2017) studied Pressure overload-induced cardiac hypertrophy and fibrosis. Pioglitazone vs. Control / GW9662 was evaluated on Cardiac hypertrophy, dysfunction, and fibrosis response to pressure overload. Pioglitazone attenuated cardiac hypertrophy, dysfunction, and fibrosis in response to pressure overload by suppressing the TGF-β/Smad signaling pathway and inhibiting EndMT via PPAR-γ activation.
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