Acetazolamide attenuates cardiac fibrosis induced by aortic constriction through inhibiting transforming growth factor-β1/Smad2 signaling pathway in mice.

The effect and mechanism of acetazolamide on cardiac fibrosis induced by transverse aortic constriction (TAC) were investigated. C57BL/6 mice were subjected to TAC or sham operation and then were orally gavaged with acetazolamide (20 mg/kg/day). After 4 weeks of operation, cardiac function was detected by echocardiography. Interstitial fibrosis was stained with Masson's trichrome. The expression of α-smooth muscle actin (α-SMA), collagen I, transforming growth factor-β1 (TGF-β1) and Smad2 were measured by western blotting. The TAC mice displayed significant cardiac dysfunction and fibrosis. The expression of α-SMA, collagen I, TGF-β1 and p-Smad2 in the TAC group was higher than those in the sham group. By contrast, acetazolamide administration inhibited interstitial fibrosis, as well as improved cardiac dysfunction induced by TAC. Acetazolamide also reduced the expression of α-SMA, collagen I, TGF-β1 and p-Smad2 in the TAC mice. Acetazolamide was able to attenuate cardiac fibrosis and improve cardiac dysfunction. The molecular mechanism involved in the anti-fibrotic effect of acetazolamide possibly was through inhibiting TGF-β1/Smad2 signaling pathway.