A novel circ_0018553 protects against angiotensin-induced cardiac hypertrophy in cardiomyocytes by modulating the miR-4731/SIRT2 signaling pathway.

ABSTRACT

Due to the complicated pathophysiology of cardiac hypertrophy, there are no effective therapies for the treatment of pathological cardiac hypertrophy. Accumulating evidence has demonstrated that circRNAs participate in the pathophysiology of cardiac hypertrophy. In this study, we investigated the regulatory mechanisms of the novel circ_0018553 in angiotensin II (Ang II)-induced cardiac hypertrophy. Circ_0018553 was enriched in endothelial progenitor cell (EPC)-derived exosomes, and circ_0018553 expression was downregulated in a cellular model of Ang II-induced cardiac hypertrophy. Silencing circ_0018553 promoted cardiac hypertrophy in the Ang II-induced cardiac hypertrophy cellular model, while overexpression of circ_0018553 significantly attenuated Ang II-induced cardiac hypertrophy in cardiomyocytes. Moreover, mechanistic studies revealed that circ_0018553 acted as a sponge for miR-4731 and that miR-4731 repressed sirtuin 2 (SIRT2) expression by targeting the 3'UTR of SIRT2. MiR-4731 overexpression promoted cardiac hypertrophy in the Ang II-induced cardiac hypertrophy cellular model, while inhibition of miR-4731 significantly attenuated Ang II-induced cardiac hypertrophy in cardiomyocytes. The rescue experiments showed that miR-4731 overexpression attenuated the protective effects of circ_0018553 overexpression on the cardiac hypertrophy induced by Ang II; SIRT2 silencing also attenuated the protective effects of miR-4731 inhibition on the Ang II-induced cardiac hypertrophy. In conclusion, our results indicated that EPC-derived exosomal circ_0018553 protected against Ang II-induced cardiac hypertrophy by modulating the miR-4731/SIRT2 signaling pathway.