Targeting mitochondrial microRNAs in cardiovascular pathologies: A new frontier in precision cardiology

Cardiovascular diseases (CVDs) continue to rise at an alarming rate, contributing to millions of deaths globally. Among them, myocardial infarction (MI), commonly known as a heart attack, remains a leading cause of mortality. Despite extensive research, MI remains incurable, and its complete eradication has yet to be achieved. Mitochondria play a central role in the pathogenesis and potential treatment of MI, and recent studies have identified mitochondrial microRNAs (mito-miRs) as promising molecular regulators. Although the precise mechanisms of mito-miRs remain incompletely understood, emerging evidence suggests their involvement in regulating mitochondrial metabolism, dynamics, ROS production, bioenergetics, and mitochondrial biogenesis. Additionally, mito-miRs influence several forms of programmed cell death, including apoptosis, necrosis, ferroptosis, and pyroptosis. The exact processes governing the translocation of these miRNAs into mitochondria and their intracellular actions remain elusive. Notably, specific miRNAs have been shown to target key cardiac cell types, including cardiomyocytes, endothelial cells, and fibroblasts. Deciphering their mechanistic roles could enable the development of targeted mito-miRNA-based therapeutics. Moreover, their therapeutic efficacy may be enhanced by integrating mito-miRs with stem cell therapies and bioactive compounds, particularly when delivered via nanoparticle-based formulations to ensure targeted delivery within the cardiac microenvironment.