Pirfenidone alleviates cardiac fibrosis induced by pressure overload via inhibiting TGF- β1/Smad3 signalling pathway

This study aims to determine the effect and mechanism of Pirfenidone (PFD), an anti-lung fibrosis medicine, in the treatment of cardiac fibrosis and heart failure induced by pressure overload. Male C57BL/6 mice were subjected to thoracic aorta constriction (TAC) or sham surgery with the vehicle, PFD (300 mg/kg/day) or Captopril (CAP, 20 mg/kg/day). After 8 weeks of surgery, mice were tested by echocardiography, and then sacrificed followed by morphological and molecular biological analysis. Compared to the sham mice, TAC mice showed a remarkable cardiac hypertrophy, interstitial and perivascular fibrosis and resultant heart failure, which were reversed by PFD and CAP significantly. The enhanced cardiac expression of TGF-β1 and phosphorylation of Smad3 in TAC mice were both restrained by PFD. Cardiac fibroblasts isolated from adult C57BL/6 mice were treated by Angiotensin II, which led to significant increases in cellular proliferation and levels of α-SMA, vimentin, TGF-β1 and phosphorylated TGF-β receptor and Smad3. These changes were markedly inhibited by pre-treatment of PFD. Collectively, PFD attenuates myocardial fibrosis and dysfunction induced by pressure overload via inhibiting the activation of TGF-β1/Smad3 signalling pathway.PMID:35861038 | DOI:10.1111/jcmm.17478
Source: J Cell Mol Med - Category: Molecular Biology Authors: Source Type: research