The circular RNA circHelz enhances cardiac fibrosis by facilitating the nuclear translocation of YAP1

Cardiac fibrosis is a common pathological change in the development of heart disease. Circular RNA (circRNA) has been shown to be related to the occurrence and development of various cardiovascular diseases. This study aimed to evaluate the effects and potential mechanisms of circHelz in cardiac fibrosis. Knockdown of circHelz alleviated cardiac fibrosis and myocardial fibroblast activation induced by myocardial infarction (MI) or angiotensin II (AngII) in vivo and transforming growth factor-fl (TGF-fl) in vitro. Overexpression of circHelz exacerbated cell proliferation and differentiation. Mechanistically, nuclear factor of activated T cells, cytoplasmic 2 (NFATc2) was found to act as a transcriptional activator to upregulate the expression of circHelz. The increased circHelz was demonstrated to bind to Yes-associated protein (YAP) and facilitate its localization in the nucleus to promote cell proliferation and growth. Moreover, silencing YAP1 reversed the detrimental effects caused by circHelz in vitro, as indicated by the observed decreases in cell viability, fibrotic marker expression levels, proliferation and migration. Collectively, the protective effect of circHelz knockdown against cardiac fibrosis injury is accomplished by inhibiting the nuclear translocation of YAP1. Thus, circHelz may be a novel target for the prevention and treatment of cardiovascular disease.

Automated summary

This study aimed to evaluate the effects and potential mechanisms of circHelz in cardiac fibrosis. The results showed that knockdown of circHelz alleviated cardiac fibrosis and myocardial fibroblast activation, while overexpression of circHelz exacerbated cell proliferation and differentiation. Mechanistically, circHelz was found to be upregulated by NFATc2 and bind to YAP to promote cell proliferation and growth. Silencing YAP1 reversed the detrimental effects caused by circHelz. Therefore, circHelz may be a novel target for the prevention and treatment of cardiovascular disease.