Inhibition of miR-499a-5p Ameliorates Apoptotic and Autophagic Damage in Hypoxic Cardiomyocytes H9c2 Through Upregulation of ARGLU1.

Myocardial infarction (MI), the most prevalent form of acute coronary syndrome, is often accompanied by cardiomyocyte apoptosis. In addition to apoptosis, autophagy plays a critical role in determining cardiomyocyte survival during MI. This study aimed to elucidate the regulatory role of miR-499a-5p in cardiomyocyte apoptosis and autophagy under hypoxic conditions. An MI mouse model was established via ligation of the left anterior descending coronary artery, and RT-qPCR was used to assess miR-499a-5p expression levels in cardiac tissues from MI and sham-operated mice. Masson's trichrome staining was employed to evaluate cardiac fibrosis, and echocardiography was conducted to assess cardiac functional parameters. For in vitro experiments, TUNEL assays and flow cytometry analyses were used to measure apoptosis and autophagy. A luciferase reporter assay confirmed the direct binding between miR-499a-5p and arginine and glutamate rich 1 (ARGLU1). Western blot analysis was used to quantify protein levels of apoptotic markers, autophagy-related proteins, and ARGLU1. The results demonstrated that MI mice developed significant cardiac fibrosis and functional impairment, along with increased miR-499a-5p expression. In H9c2 cells, knockdown of miR-499a-5p significantly reduced hypoxia-induced apoptosis and autophagy, whereas miR-499a-5p overexpression exacerbated these processes. Moreover, ARGLU1 was identified as a direct target of miR-499a-5p and was negatively regulated by it. Silencing ARGLU1 enhanced hypoxia-induced apoptosis and autophagy and reversed the protective effects observed with miR-499a-5p knockdown. In summary, miR-499a-5p inhibition mitigates hypoxia-induced injury in H9c2 cells by reducing apoptosis and autophagy through the upregulation of ARGLU1, suggesting a potential therapeutic target for MI.