ABUNDANT EXPRESSION OF APOPROTEIN-E BY MACROPHAGES IN HUMAN AND RABBIT ATHEROSCLEROTIC LESIONS

Previous studies have demonstrated the presence of apoprotein (apo) E protein and message in arterial lesions. To determine the source of th e synthesized apoE, we performed simultaneous in situ hybridization an d immunocytochemistry on human and rabbit atherosclerotic tissue. Stud ies of serial sections of aortic atherosclerotic lesions from humans a nd hypercholesterolemic New Zealand White rabbits and Watanabe heritab le hyperlipidemic rabbits revealed a similar pattern of macrophage-spe cific apoE expression in the rabbit and human lesions. In early lesion s of rabbit atherosclerotic tissue, in which many macrophages were pre sent, there was abundant expression of apoE mRNA. Northern blot analys es of total mRNA obtained from arterial macrophage-derived foam cells, freshly isolated from ballooned, cholesterol-fed New Zealand White ra bbits, demonstrated positive hybridization with an apoE-specific ribop robe. Western blot analyses of conditioned media from the isolated foa m cells placed in culture for up to 24 hours demonstrated the presence of secreted apoE. These studies demonstrated that in atherosclerotic lesions, arterial wall macrophages synthesize and secrete apoE and pro bably account for most of the apoE synthesized in the atherosclerotic artery.