Based on the in vitro and in vivo experiments, the present study presented that macrophage-secreted EVs carrying miR-503-5p inhibits proliferation, migration, and angiogenic potentials of HCAECs, while accelerating the proliferation and migration of HCASMCs in atherosclerosis via TGF-β/smad7/smurf1/smurf2 axis. Here, SMAD7 is linked to atherosclerosis.