Objective To investigate the effects and mechanisms of cyclin-dependent kinase (CDK) inhibitor R547 on myocardial fibrosis in mice with transverse aortic constriction (TAC).

Methods The C57BL/6J male mice were used to establish a TAC model, and randomly divided into sham operation group (Sham group), R547 group, TAC group and TAC + R547 group. The R547 group were intraperitoneally injected with 10 mg/kg R547 (once every other day for 3 weeks). After 3 weeks of surgery, the cardiac function was assessed by echocardiography, the fibrosis levels were observed by HE/Masson staining, and the protein expression levels of CDK1/2/4, Collagen I and transforming growth factor-β (TGF-β)/Smad3 were detected by Western blotting.

Results Compared with the Sham group, the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and left ventricular anterior/posterior wall thickness (LVAWd/LVPWd) significantly increased in the TAC group (P ＜ 0.01). There were statistical differences in the LVEF, LVFS and LVAWd/LVPWd between the TAC + R547 group and Sham group (P ＞ 0.05). Histologically, the fibers in the TAC + R547 group were arranged more regularly, and the collagen deposition was reduced compared with the TAC group (P ＜ 0.01). The results of Western blotting showed that protein expression levels of CDK1/2/4, Collagen I, and TGF-β/Smad3 pathways were significantly downregulated in the TAC + R547 group (P ＜ 0.01).

Conclusions R547 alleviates TAC-induced myocardial fibrosis by inhibiting CDK1/2/4 and regulating the TGF-β/Smad3 signaling pathway.