Endothelial miR-199a-3p regulating cell adhesion molecules by targeting mTOR signaling during inflammation

Abstract

BackgroundAdherence of monocytes to endothelial cells is the initial stage for development of coronary artery disease (CAD). MiRNAs have been reported to participate in this process by regulating the expression of cell adhesion molecules. This study aimed to explore the function of miR-199a-3p in endothelial inflammation and adhesion. MethodsWe assessed the expression of miR-199a-3p in CAD patients and ApoE-/- mice. The relationship between miR-199a-3p level and endothelial inflammation and adhesion was examined. ELISA was used to test the level of IL-6 and IL-8. Dual luciferase reporter assay was used to evaluate the binding between miR-199a-3p and mTOR. ResultsA decreased expression of miR-199a-3p was observed in the PBMCs and plasma of CAD patients, aorta of ApoE-/- mice and inflammatory HUVECs. MiR-199a-3p significantly suppressed the expression levels of pro-inflammatory cytokine (IL-6, IL-8), endothelial adhesion molecules (ICAM-1, VCAM-1) and monocyte-endothelial cells interaction. MiR-199a-3p directly targeted and repressed mTOR, and its suppression effect on ICAM-1 and VCAM-1 was abolished by mTOR inhibitor rapamycin, and rescued by mTOR activator MHY1485. Overexpression of miR-199a-3p promoted autophagy in HUVECs and inhibiting autophagy by chloroquine attenuated the effect of miR-199a-3p on ICAM-1 and VCAM-1 expression. Inhibition of autophagy promoted endothelial adhesion molecule expression and monocyte-EC interaction. ConclusionsOur results suggested that miR-199a-3p suppressed endothelial inflammation and adhesion by targeting mTOR signaling and increasing autophagy. Our findings point to an important role for miR-199a-3p in the early stage of cardiovascular disease.