In severe hypercholesterolemia, uptake of ox-LDL by circulating monocytes (through scavenger receptors and undefined pathways) activates monocytes, and drives CD11c--to-CD11c+ monocyte differentiation, forming CD11c+ “foamy monocytes.” These CD11c+ “foamy monocytes” express high levels of VLA-4 and CD11b, and adhere efficiently to ECs through interactions of CD11c and VLA-4 with VCAM-1 on activated ECs, thereby playing an active role in development of atherosclerosis and xanthomas associated with severe hypercholesterolemia.