Plasma exosomes from patients with stable coronary artery disease significantly increased endothelial permeability and atherosclerotic lesion area in vivo by transferring miR-140-3p, which suppresses ZO-1 expression.
Plasma exosomes from patients with stable coronary artery disease promote atherosclerosis by impairing endothelial junctions via miR-140-3p-mediated suppression of ZO-1.
p-value: p=<0.001
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 (Exo SCAD ) contain differentially expressed miRNAs that are clustered with genes related to cell junctions, prompting us to investigate the role of Exo SCAD in regulating vascular endothelial junctions and to elucidate the underlying mechanisms. Here, we show that Exo SCAD 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 Exo SCAD -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.
Han et al. (Sat,) conducted a other in Stable coronary artery disease (SCAD) (n=78). Plasma exosomes from SCAD patients (ExoSCAD) vs. Plasma exosomes from healthy controls (ExoHC) or PBS was evaluated on Endothelial permeability and atherosclerotic lesion area (p=<0.001). Plasma exosomes from patients with stable coronary artery disease significantly increased endothelial permeability and atherosclerotic lesion area in vivo by transferring miR-140-3p, which suppresses ZO-1 expression.