Plasma exosomal miR-483-3p induces myocardial injury by suppressing autophagy via targeting XPO1 in OSA.

AIMS

Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular diseases, closely associated with myocardial injury, yet its underlying mechanisms remain unclear. Plasma exosomes, known to regulate cellular processes by transporting microRNAs (miRNAs), have been implicated in OSA-induced endothelial dysfunction. However, their role in OSA-induced myocardial injury remains unclear.

MATERIALS AND METHODS

Plasma exosomes were isolated from plasma of non-OSA controls (CON-Exos) and OSA patients (OSA-Exos) using differential centrifugation. The exosomes were co-cultured with myocardial cells or administered to mice via the tail vein injections. High-throughput sequencing and RT-PCR screened for enriched miRNAs in OSA-Exos, with bioinformatics predicting target genes. The role of target miRNAs in myocardial injury was validated through in vivo and in vitro experiments, and the correlation between target miRNAs and myocardial injury markers in the plasma exosomes of OSA patients was analyzed.

KEY FINDINGS

Plasma exosomes from OSA patients were found to deliver miR-483-3p into myocardial cells, where it downregulated XPO1, inhibited autophagy, and induced myocardial hypertrophy. This process elevated myocardial injury markers, and impaired cardiac function. Levels of plasma exosomal miR-483-3p were positively correlation with myocardial injury markers in OSA patients.

SIGNIFICANCE

Exosome miR-483-3p from OSA downregulates the expression of XPO1 in cardiomyocytes, thereby modulating autophagy and contributing to myocardial injury. This study provides new mechanistic insights into the molecular pathways underlying OSA-induced cardiac damage and identifies miR-483-3p as a potential biomarker and therapeutic target.