Concurrent endothelial cell turnover and leukocyte margination in early atherosclerosis

Leukocyte margination and migration into nascent atherosclerotic lesion have been suggested as two early events in aortic atherosclerosis. It has also been suggested that altered endothelial cell function may mediate the margination process. In this paper we present quantitative data on leukocyte adherence to the luminal aspect of the aortic endothelium and correlate it with severity of atherosclerosis and extent of endothelial cell turnover. Both naturally occurring and cholesterol induced atherosclerotic lesions were studied. The sites of endothelial cell turnover were determined by scanning electron microscope whole mount autoradiography of 3H-thymidine labeled aortas. Morphometric analysis of atherosclerosis severity and leukocyte adhesion was accomplished by stereological analysis of conventional SEM preparations. Leukocyte adherence was localized in atherosclerosis susceptible areas of the aorta and increased dramatically over atherosclerotic lesions. Endothelial cell turnover also increased in atherosclerotic areas as indicated by an increase in the number of labeled nuclei found over lesions. Both leukocyte adherence and endothelial cell turnover occurred over the entire extent of the lesions studied, but were particularly prevalent at the growing edge of the lesions.