Tanshinone IIA exerts antifibrotic effects in postinfarct cardiac fibrosis. - GreenMedInfo Summary
microRNA-29b Mediates the Antifibrotic Effect of Tanshinone IIA in Postinfarct Cardiac Remodeling.
J Cardiovasc Pharmacol. 2015 May ;65(5):456-64. PMID: 25636075
BACKGROUND: Tanshinone IIA (TSN) is one of the main components isolated from Danshen, which is widely used for the treatment of cardiovascular diseases. The transforming growth factor beta (TGF-β) signaling pathway and microRNA (miR)-29b play important roles in the progression of cardiac fibrosis and the modulation of cardiac fibroblast (CF) function. Our study investigated the role of miR-29b in the cardioprotective effects of TSN in postinfarct cardiac remodeling.
METHODS AND RESULTS: Echocardiography demonstrated that medium-dose TSN (TSN-M) and high-dose TSN (TSN-H) significantly inhibited postinfarct cardiac fibrosis and improved the impaired left ventricular function in rats subjected to acute myocardial infarction. Moreover, quantitative real-time polymerase chain reaction and Western blot demonstrated that TSN-M and TSN-H downregulated the expression of TGF-β1, Col1a1, Col3a1, and α-SMA but upregulated the expression of miR-29b. CFs treated with TSN showed inhibited TGF-β signaling pathway, downregulated expression of Col1a1, Col3a1, and α-SMA, and upregulated miR-29b expression in vitro. Furthermore, treatment with a miR-29b inhibitor dramaticallyinhibited these TSN-induced antifibrotic effects, suggesting that miR-29b may be responsible for the antifibrotic effects of TSN. In addition, treatment with Smad3 siRNA significantly inhibited miR-29b expression in CFs, which implies that Smad3 signaling promotes miR-29b expression on CFs.
CONCLUSIONS: TSN exerts antifibrotic effects in postinfarct cardiac fibrosis by upregulating the expression of miR-29b, which is mediated by the TGF-β-Smad3 signaling pathway.