Additional puzzling observations come from immune cell-mediated disease models such as experimental autoimmune encephalomyelitis (EAE) (24), collagen-induced arthritis (86, 87), or atherosclerosis in low density lipoprotein receptor (LDLR)- or apolipoprotein E (ApoE)-deficient mice (88, 89), in which absence of PECAM-1 was found to lead to aggravated disease severity. This evidence concerns the gene APOE and atherosclerosis.