The vascular endothelial cell is generally small and round and has a single small nucleus. It is called a typical endothelial cell (TEC). In human aortas, however, unusually large endothelial cells are often seen. They have multinuclei in a large cytoplasm and are called multinucleated variant endothelial cells (MVECs). MVECs exist individually or in a group, being surrounded by the majority of typical endothelial cells. The number of MVECs is increased with atherosclerosis grade and age. FISH analysis revealed that endothelial cells derived from young subjects had diploid chromosomes. However, aneuploidy was increased with aging in TECs as well as in MVECs, ranging from one to five or even more than five. Expression of LDL receptor on endothelial cells was generally low but greatly elevated in MVECs. Accordingly the uptake of LDL cholesterol was increased when observed in LDL-gold uptake by electron microscopy, whereas those of TECs remained low. These results indicate that human aortic endothelial cells change their characteristics, including shape and even gene, with aging, and that MVECs appear on the human aorta. MVECs actively participate in the development and advancement of atherosclerosis by transporting LDL to the subendothelial intima.