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 initiate d by hypoperfusion or thrombotic occlusion of the adventitial vasa vas onum. Design: In a new model of atherogenesis, an early atheroscleroti c lesion may be initiated by removal of the adventitia from the caroti d artery of the New Zealand White rabbit, wherein lie the vasa vasorum . Setting: Animal laboratory, University Department of Surgery and Med icine. Materials: 15 rabbits fed a normal diet and 32 fed a high chole sterol diet. Chief Outcome Measures: Immunocytochemistry was undertake n to demonstrate the presence of smooth muscle cells and macrophages w ithin the intimal lesions. Smooth muscle cells were labelled with a mo noclonal 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 compo sed exclusively of smooth muscle cells. By day 28, such lesions had re gressed. In rabbits fed a high cholesterol diet, at day 14, the intima l lesion was composed of a mixture of macrophages and smooth muscle ce lls. By day 42, the pattern of cellular distribution was such that mac rophages (present as foam cells) were predominant. In the presence of persistent hypercholesterolaemia these lesions did not regress. Conclu sions: This new model can produce two different cellular responses tha t may mimic the intimal lesions seen with re-stenosis after angioplast y or in hypercholesterolaemic man and as such, might be useful in sepa rating out these two different pathophysiologies.