INTRODUCTION: Myocardial fibrosis (MF) is a key pathological change in heart failure, and lactate a product of glycolysis, is an important component affecting the process of MF. miRNAs derived from METHODS: A mouse model of MF was established by subcutaneous infusion of Ang II using osmotic pumps, and then administration of Gen-miR-5 by injection. The effects of Gen-miR-5 in reducing MF and exerting cardioprotective actions were evaluated through pathological morphological analysis and echocardiography. The targeting effect of Gen-miR-5 on PFKP was assessed through dual-luciferase reporter gene assays. Cardiac fibroblasts (CFs) migration abilities were evaluated through wound healing assay and transwell assays. Additionally, the role of Gen-miR-5 in fibroblast activation was investigated using gain- and loss-of-function experiments, and immunofluorescence. RESULTS: This study identified six novel specific miRNAs in DISCUSSION: In conclusion, we have elucidated for the first time the pharmacological effects of Gen-miR-5, derived from