Insights Into Remote Ischemic Conditioning <scp>miRNA</scp> Effects on Brain Endothelial Cells During Ischemia–Reperfusion

OBJECTIVE: Acute ischemic stroke (AIS) is one of the leading causes of death and disabilities, and as such, it is of utmost importance to identify novel treatment options. Remote ischemic conditioning (RIC) is a promising non-invasive treatment that is thought to activate the body's own protective mechanisms against damaging ischemia. Here, we study the transcriptomic impact of microRNAs (miRNAs) that are upregulated by RIC. METHODS: Using RNA sequencing, we investigated the transcriptional changes in human brain microvascular endothelial cells (HBMECs) transfected with four selected RIC-upregulated miRNAs (RIC-miRNAs), miR-16-5p, miR-144-3p, miR-182-5p, and miR-451a, under oxygen and glucose deprivation (OGD) and reoxygenation-mimicking the initial stages of AIS. RESULTS: Pronounced transcriptional changes were present after RIC-miRNA transfection, with 149 unique downregulated and 212 upregulated differentially expressed genes in HBMECs after OGD and RIC-miRNA transfection compared to all other conditions. These genes were involved in pathways of energy metabolism and cell cycle regulation. CONCLUSION: Our study suggests that the selected RIC-miRNAs regulate pathways that may facilitate endothelial cell survival, recovery, and remodeling events from ischemic damage, adding to the knowledge of the pathways affected by RIC during stroke.