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

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Traditional Chinese Medicine

Background:

• Abnormal exosome-miRNA intercellular communication drives myocardial energy metabolism disorders and ventricular remodeling in heart failure (HF).
• Renshen Decoction (RSD), a traditional formula, shows cardioprotective effects, but its mechanism in HF via exosome-miRNA regulation is unknown.

Purpose of the Study:

• To investigate how RSD improves myocardial energy metabolism disorders and inhibits ventricular remodeling in HF by regulating exosome-miRNAs.

Main Methods:

• In vivo studies in HF rats assessed RSD's effects on myocardial energy metabolism and ventricular remodeling.
• Exosomal miRNA sequencing of peripheral blood identified key miRNAs affected by RSD in HF.
• In vitro experiments used endothelin-1 stimulated cardiac fibroblasts (CFs) and co-cultured CF-derived exosomes with cardiomyocytes (CMs) to validate RSD's regulatory effects.

Main Results:

• RSD ameliorated myocardial energy metabolism disorders and inhibited ventricular remodeling in HF rats.
• Exosomal miRNA sequencing identified miR-30e-5p as a key miRNA targeted by RSD.
• RSD inhibited cardiomyocyte injury induced by CF-derived exosomes carrying miR-30e-5p and suppressed downstream targets (RARβ, SIRT1, BDNF, FTO).

Conclusions:

• RSD improves cardiomyocyte energy metabolism by regulating the CFs-EXOs-miR-30e-5p-RARβ/SIRT1/BDNF/FTO pathway.
• This pathway regulation by RSD inhibits ventricular remodeling in heart failure.
• The findings suggest RSD as a novel therapeutic strategy for heart failure.