A three-step approach identifies novel shear stress-sensitive endothelial microRNAs involved in vasculoprotective...

Circulatory microRNAs (c-miRNAs) are regulated in response to physical activity and may exert anti-atherosclerotic effects. Since the vascular endothelium is an abundant source of c-miRNAs, we aimed to identify novel vasculoprotective exercise-induced c-miRNAs by the combined analysis of published endothelial miRNA array data followed by in vivo and in vitro validation. We identified 8 different array-based publications reporting 185 endothelial shear stress-regulated miRNAs of which 13 were identified in ≥3 independent reports. Nine miRNAs had already been associated with physical activity. Of the remaining novel miRNAs, miR-98-3p and miR-125-5p were selected for further analysis due to reported vasculoprotective effects. Analysis in two different 4-week high-intensity interval training (HIIT) groups (group 1 [n=27]: 4x30 s, group 2 [n=25]: 8x15 s; all-out running) suggested significantly elevated miR-98 and miR-125a-5p levels in response to acute exercise at baseline and at follow-up. Endothelial in vitro shear stress experiments revealed increased miR-125a-5p and miR-98-3p levels in medium of human umbilical vein endothelial cells at 30 dyn/cm² after 20 and 60 min, respectively. Our results suggest that miR-98-3p and miR-125a-5p can be rapidly secreted by endothelial cells, which might be the source of increased c-miR-98-3p and -125a-5p levels in response to HIIT. Both miRNAs attenuate endothelial inflammation and may mediate vasculoprotective effects of physical exercise including HIIT.