Exploring the protective potential of remote ischemic conditioning-induced miRNAs in stroke

Remote ischemic conditioning (RIC) is a non-invasive strategy that mitigates ischemic injury, partly through circulating microRNAs. Emerging evidence suggests that miRNAs may modulate angiogenesis, which is essential for post-stroke recovery. This study investigated the effect of four RIC-induced miRNAs (RIC-miRNAs), miR-16-5p, miR-144-3p, miR-182-5p, and miR-451a, in immortalized human brain microvascular endothelial cells (IM-HBMECs) exposed to inflammatory conditions in vitro. Transcriptomic and in silico analysis were used to identify target genes of RIC-miRNAs. Two angiogenesis-related genes, SLIT2 and TEK, were validated in vitro. as functional targets of miR-16-5p and miR-144-3p, respectively. Rare variant burden analyses in UK Biobank data associated TEK variants with reduced ischemic stroke risk and regulatory SLIT2 variants with increased stroke risk. Functional enrichment analysis further linked the RIC-miRNA-associated targets to the regulation of apoptotic processes, cytokine production, and sprouting angiogenesis. These findings suggest that miR-16-5p and miR-144-3p may modulate endothelial pathways involved in cell death, inflammatory signaling, and vascular remodeling during the response to stroke.