Vinchi and his team were the first to prove the connection between nontransferrin bound serum iron (NTBI) and AS by investigating a mouse model (ApoE-/- FPNwt/C326S), they observed that iron is heavily deposited in the arterial media layer in the presence of elevated NTBI, induces ROS production, apoptosis of SMCs and ECs, and stimulates a large number of MCP-1-mediated monocyte recruitment, formation of unstable plaques, and eventually aggravates atherosclerosis [48, 49]. Here, APOE is linked to atherosclerosis.