In addition, double knockout ApoE −/− TLR-4 −/− mice demonstrated a significant reduction in atherosclerosis compared to ApoE −/− mice [22], and the administration of LPS (a typical TLR-4 ligand) to the adventitial surface of murine arteries increased atherosclerosis compared to control, implicating the adventitia in lesion progression [23]. Here, APOE is linked to atherosclerosis.