Upregulation of miR-93 and inhibition of LIMK1 improve ventricular remodeling and alleviate cardiac dysfunction in rats with chronic heart failure by inhibiting RhoA/ROCK signaling pathway activation

摘要

Objective: There are some researches about the role of microRNA (miRNA) in chronic heart failure (CHF) were performed, but the study about miR-93’s function in CHF is scarcely investigated. Thus, we determined to probe into the effects of miR-93 in rats with CHF by targeting LIMK1 through regulating RhoA/ROCK pathway.Results: We found increased LIMK1 and decreased miR-93 in CHF rats, and up-regulation of miR-93 inhibited LIMK1, RhoA and ROCK1 expression in CHF rats. Up-regulation of miR-93 or inhibition of LIMK1 decreased oxidative stress, inflammatory factors, as well as apoptosis-related indicators in CHF rats. LIMK1 was confirmed as a direct target gene of miR-93.Conclusion: Our study provides evidence that upregulated miR-93 and downregulated LIMK1 improve ventricular remodeling and reduce cardiac dysfunction in CHF rats by inhibiting RhoA/ROCK signaling pathway activation.Methods: First, rat models of CHF were established by aortic coarctation, and the rats were injected with miR-93 mimics, LIMK1-siRNA or overexpressed-LIMK1. Then expression of miR-93, LIMK1, RhoA, and ROCK1 expression in myocardial tissues were detected, after which indices of cardiac ultrasound, hemodynamics, and oxidative stress, inflammatory factors, apoptosis-related indicators were detected via a series of assays. Finally, the targeting relationship of miR-93 and LIMK1 was verified.