Renshen decoction improves myocardial energy metabolism in heart failure by regulating exosomal miR-30e-5p

Abstract

Background: Abnormal intercellular communication mediated by exosome (EXOs)-miRNAs in cardiac cells is the core pathogenic mechanism that induces myocardial energy metabolism disorders and leads to ventricular remodeling in heart failure (HF). Renshen Decoction (RSD), a traditional formula, exerts significant cardioprotective effects. However, whether it inhibits ventricular remodeling in HF by regulating EXOs-miRNA-mediated intercellular communication remains unclear.

Objective: To explore the mechanism by which RSD improves myocardial energy metabolism disorders and inhibits ventricular remodeling in HF by regulating EXOs-miRNAs.

Methods: In vivo experiments were conducted to observe the inhibitory effects of RSD on myocardial energy metabolism and ventricular remodeling in HF rats. Exosomal miRNA sequencing was performed using peripheral blood samples to screen for key EXOs-miRNAs mediating the effects of RSD on HF. In vitro, cardiac fibroblasts (CFs) were stimulated with endothelin-1. CF-derived EXOs were extracted and co-cultured with cardiomyocytes (CMs) to investigate the targeted regulatory effects of RSD on the candidate CFs-EXO-miRNA.

Results: RSD inhibited ventricular remodeling in HF rats by ameliorating myocardial energy metabolism disorder. Peripheral blood EXOs-miRNA sequencing identified miR-30e-5p as a key miRNA targeted by RSD. In vitro experiments revealed that RSD inhibited cardiomyocyte injury induced by CFs-EXOs-miR-30e-5p Additionally, RSD suppressed the abnormally high expression of the downstream targets of miR-30e-5p, including RARβ, SIRT1, BDNF, and FTO, in HF pathology.

Conclusion: This study is the first to demonstrate that RSD may improve the energy metabolism disorder of CMs by regulating the CFs-EXOs-miR-30e-5p-RARβ/SIRT1/BDNF/FTO pathway, thereby inhibiting HF ventricular remodeling, which may provide new ideas for the treatment of HF.

Keywords: Cardiac fibroblasts and cardiomyocytes; Exosomes; Heart failure; Renshen decoction; miR-30e-5p-RARβ/SIRT1/BDNF/FTO.