Empagliflozin modulates microRNA expression in human primary cardiomyocytes under CoCl₂-induced hypoxia

Cardiovascular diseases (CVD) remain the leading cause of premature death worldwide, with a steadily rising incidence. Ischemia, characterized by insufficient blood flow and subsequent tissue hypoxia, contributes significantly to cellular damage, dysfunction, as well as epigenetic alterations in CVD. Hypoxia-induced epigenetic changes have been associated with fibrosis, inflammation, metabolic dysregulation, and altered programmed cell death in cardiac tissue. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor primarily prescribed for type 2 diabetes, has also demonstrated beneficial effects in patients with CVD.

The present study aimed to evaluate the protective role of Empagliflozin in primary human cardiomyocytes under chemically induced hypoxia, with a focus on its influence on specific microRNAs. Cardioprotective effects were analyzed through the expression of miR-214-3p, miR-22-5p, miR-103-5p, and miR-145-5p, along with protein levels of GAPDH and HIF1α.

After 24 h of Empagliflozin treatment, a significant upregulation of the cardioprotective miR-214-3p (p < 0.05) was observed. These findings demonstrate a direct cardioprotective effect of Empagliflozin in cobalt-treated cardiomyocytes and suggest its potential role as an epigenetic modulator in the pathogenesis of CVD.