Multinucleated variant endothelial cells (MVECs) of human aorta: Expression of tumor suppressor gene p53 and relationship to atherosclerosis and aging

Multinucleated variant endothelial cells (MVECs) generally exist in atheros clerotic human aorta and even in nonatherosclerotic aorta. Because the numb er of nuclei is increased in every MVEC, and because DNA instability was su spected, a series of oncogene expressions was conducted to clarify the natu re of nuclear abnormality. The tumor suppressor gene p53 was found to be sp ecifically expressed in the multinuclei of MVECs, while double nuclei were sometimes positive, and mononuclear typical endothelial cells were always n egative for p53. Polymerase chain reaction-single-strand conformation polym orphism (PCR-SSCP) revealed extra bands in exons 5 and 7 of the p53 gene, b ut no additional band in exons 6 and 8. In a BCL familiy, BCL-2 was coexpre ssed in one or two nuclei in the perinuclear space of the multinuclei of MV ECs, whereas MCL-1, BCL-XS/L, and BAX were all negative, indicating that th e BCL-2 coding gene is expressed only in the corresponding one or two nucle i of the multinuclei. Another oncogene, c-MET (hepatocyte growth factor rec eptor), was universally expressed in either type of endothelial cells, but other oncogenes, k-RAS and c-ERBB2, were not expressed in either type. MVECs were derived from human aorta and therefore non-tumorous somatic cell s. No morphologic evidence of apoptosis was found. Although it is unclear t hat the extra bands came from the MVECs or just from ECs associated with at herosclerosis, combined immunocytological studies and PCR analysis suggest that MVECs express mutant type p53.