Macrophage and smooth muscle cell proliferation in atherosclerotic lesions of WHHL and comparably hypercholesterolemic fat-fed rabbits.

Abstract

Lesions of atherosclerosis were analyzed at varying stages of development in Watanabe heritable hyperlipidemic (WHHL) and comparably hypercholesterolemic fat-fed (FF) rabbits for the capacity to incorporate thymidine into proliferating cells within both the intima and the underlying media. An identical inverse relationship between the intimal/medial ratio (which reflects both lesion size and severity) and the labeling index was observed for both the WHHL and FF rabbits. Analysis of the spatial distribution of the labeled cells within each lesion revealed the highest rates of thymidine incorporation in cells situated within the superficial areas and lateral margins of the lesions. Up to 12% of the labeled cells were foam cells, which were predominantly located immediately beneath the endothelium and within the lateral margins. Some labeled macrophages were also observed within the necrotic core of advanced lesions. There were no differences in the labeling indexes at differing sites in the aorta, providing lesions of comparable size were compared. Simultaneous thymidine autoradiography and immunostaining with cell type-specific monoclonal antibodies revealed that approximately 30% of the labeled cells were macrophages and 45% were smooth muscle cells in advanced lesions from both WHHL and FF rabbits.