Aim: MicroRNA-10a (miR-10a) is a miR with the lowest expression in the athero-susceptible regions in normal adult swine. The present study used pathogenic condition to identify the relationship between miR-10a and atherosclerosis, with the goals of developing the clinical application of miR-10a for atherosclerosis. Methods: We combine in vitro flow system, in vivo experimental animals, and human specimens with coronary artery disease (CAD) to examine the functional role of miR-10a and its diagnostic and therapeutic application in atherosclerosis. Results: We find that miR-10a levels in both aortic endothelium of atherosclerotic lesions and blood plasma from ApoE-knockout mice and CAD patients are decreased. The down-regulation of endothelial miR-10a in human atherosclerotic lesions is accompanied by the strong expressions of its downstream molecules GATA6/VCAM-1. The combined usage of RARα- and RXRα-specific agonists exerts additive effects on rescuing oscillatory shear-inhibited miR-10a expression to repress GATA6/VCAM-1 in ECs in vitro. The effect of RARα/RXRα-specific agonists on rescuing miR-10a is confirmed in vivo on rats by en face staining. Induction of endothelial miR-10a in vivo by administrating RARα/RXRα-specific agonists protects ApoE-knockout mice from atherosclerosis through inhibiting GATA6/VCAM-1 and inflammatory cell infiltration in the atherosclerotic vessel wall. The safety of in vivo miR-10a induction is validated by blood chemistry, urine, and mortality rate analyses. Conclusions: Our findings identify that decreased miR-10a levels in aortic endothelium and blood serum are highly related to atherogenesis and have potential to be developed as diagnostic molecule for atherosclerotic disease. Moreover, RARα/RXRα-specific agonists are potential hemodynamics-based components for atherosclerosis treatment.
