Endothelial dysfunction, and the differentiation of smooth muscle cells (SMCs) into proliferative, secretory phenotypes, are two major pathophysiological processes in atherosclerosis. SMCs have the potential to recruit macrophages in atherosclerotic plaques, in which macrophages drive inflammatory responses. In this study, we found that microRNA-503-5p (miR-503-5p) was enriched in either extracellular vesicles (EVs), secreted by oxidized low-density lipoprotein-treated macrophages, or the EVs from peripheral blood mononuclear cells of atherosclerosis patients. miR-503-5p was transferred intercellularly from macrophages to the co-cultured human coronary artery endothelial cells (HCAECs) and HCASMCs via EVs, thus reducing the proliferative and angiogenic abilities of HCAECs and accelerating the proliferative and migrating abilities of HCASMCs. Smad family members 1, 2 and 7 were negatively regulated by miR-503-5p in HCAECs and HCASMCs. miR-503-5p was verified as an enhancer of inflammatory cytokines and adhesion molecules released by macrophages, in part via the down-regulation of smad family members 1, 2 and 7. The inhibition of miR-503-5p by lentivirus reduced atherosclerotic lesion formations in the aorta of atherosclerotic mice. Our work demonstrated a miR-503-5p- and EV-mediated mechanism for macrophage communication with HCAECs and HCASMCs in atherosclerosis. miR-503-5p is pro-atherosclerotic stimuli that may be a therapeutic target for atherosclerosis treatment.
Keywords: atherosclerosis; endothelial cells; extracellular vesicle; macrophage; microRNA-503-5p.