Curcumin attenuates pressure overload-induced cardiac fibrosis in mice via modulating the miR-29b/HDAC4 axis

To investigate the antifibrotic effects of curcumin in a transverse aortic constriction (TAC) mouse model and elucidate its molecular mechanisms. Male C57BL/6 mice underwent TAC and received vehicle, low-dose curcumin (50 mg/kg), high-dose curcumin (200 mg/kg), high-dose curcumin plus a scrambled control antagomir, or high-dose curcumin plus anti-miR-29b treatments. Cardiac function was assessed by echocardiography. Fibrosis was evaluated by histology, collagen volume fraction, and hydroxyproline content. Expression of miR-29b, HDAC4, and fibrosis-related markers (Collai, Col3a1, TGF-β1) was measured by quantitative RT-PCR and Western blotting assays. Myocardial procollagen type I carboxyterminal propeptide was determined by ELISA, and HDAC4-specific enzymatic activity was assayed using a fluorogenic kit. Curcumin improved cardiac function, reduced fibrosis, restored miR-29b expression, and suppressed HDAC4 expression and activity in a dose-dependent manner. Furthermore, curcumin decreased myocardial procollagen type I carboxy-terminal propeptide levels, confirming reduced collagen synthesis. Anti-miR-29b administration partially abrogated the antifibrotic and cardioprotective effects of curcumin. Curcumin attenuates pressure overload-induced cardiac fibrosis and dysfunction in a TAC mouse model via modulation of the miR-29b/HDAC4 axis and suppression of collagen synthesis.