Lara Marziani, Katrine Tang Stenz, Hao Zhang, Weixiang Zhao, Birgitte Hviid Mumm, Xie Dong-Fang, Minxian Wang, Xiu-Jie Wang, Kim Ryun Drasbek
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. 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.