Taken together, this study reveals that macrophage-derived EVs carrying miR-503-5p can inhibit proliferation, migration, and angiogenic ability of HCAECs, while promoting the proliferation and migration of HCASMCs by downregulating Smad7, smurf1, and smurf2 and elevating TGF-β1, thus aggravating atherosclerosis. Here, SMAD7 is linked to atherosclerosis.