Abstract
The underlying mechanism of vascular endothelial hyperpermeability caused by decrease of endothelial junctions occurring in atherosclerosis remains elusive. Our findings identified that plasma exosomes from patients with stable coronary artery disease (ExoSCAD) contain differentially expressed miRNAs that are clustered with genes related to cell junctions, prompting us to investigate the role of ExoSCAD in regulating vascular endothelial junctions and to elucidate the underlying mechanisms. Here, we show that ExoSCAD markedly impair vascular endothelial junctions via suppressing VE-Cadherin and ZO-1 in endothelial cells in vitro and in vivo, consequently increases endothelial permeability. Critically, exosomal miR-140-3p plays a crucial role in ExoSCAD-induced inhibition of ZO-1, and may be an important causative factor in the development of endothelial hyperpermeability during atherosclerosis. Additionally, exosomal miR-140-3p level coordinates with severity of SCAD. Targeting miR-140-3p in circulating exosomes might open novel options for treatment of atherosclerosis.