THE INFLUENCE OF THE ADVENTITIA ON THE PRESENCE, OF SMOOTH-MUSCLE CELLS AND MACROPHAGES IN THE ARTERIAL INTIMA

Objective: To test the hypothesis that atherosclerosis may be initiated by hypoperfusion or thrombotic occlusion of the adventitial vasa vasonum. Design: In a new model of atherogenesis, an early atherosclerotic lesion may be initiated by removal of the adventitia from the carotid artery of the New Zealand White rabbit, wherein lie the vasa vasorum. Setting: Animal laboratory, University Department of Surgery and Medicine. Materials: 15 rabbits fed a normal diet and 32 fed a high cholesterol diet. Chief Outcome Measures: Immunocytochemistry was undertaken to demonstrate the presence of smooth muscle cells and macrophages within the intimal lesions. Smooth muscle cells were labelled with a monoclonal antibody designated HHF35 and macrophages were labelled with a rabbit specific, macrophage specific antibody, RAM11. Chief Results: In rabbits fed a normal diet, at day 14, the intimal lesion was composed exclusively of smooth muscle cells. By day 28, such lesions had regressed. In rabbits fed a high cholesterol diet, at day 14, the intimal lesion was composed of a mixture of macrophages and smooth muscle cells. By day 42, the pattern of cellular distribution was such that macrophages (present as foam cells) were predominant. In the presence of persistent hypercholesterolaemia these lesions did not regress. Conclusions: This new model can produce two different cellular responses that may mimic the intimal lesions seen with re-stenosis after angioplasty or in hypercholesterolaemic man and as such, might be useful in separating out these two different pathophysiologies.