Cholesterol-induced atherosclerosis. Clonal characteristics of arterial lesions in the hybrid hare.

Utilizing the observation that a majority of human atherosclerotic fibrous plaques show monoclonal characteristics, we carried out this study to determine the clonal characteristics of cholesterol-induced atherosclerosis in the hybrid hare. If this is a valid model for human atherosclerosis, the lesions produced in the aorta should be monoclonal. Glucose-6-phosphate dehydrogenase (G-6-PD) was used as an X-linked cellular marker in the female hybrid hare (Lepus timidus X Lepus europaeus), which is heterozygous for electrophoretically separable isoenzymes of G-6-PD. Hares were fed cholesterol over either a 6-month or a 16-month period, and the easily dissectable lesions in the aorta and common iliac arteries were assayed for isoenzyme activity at these times. Of the 93 lesions assayed, all had polyclonal characteristics except a single monoclonal lesion found in an animal fed cholesterol over a 16-month period. Hares fed over the 16-month period showed lesions with isoenzyme patterns having a significantly higher contribution of L. timidus isoenzyme than those found in underlying media. This suggested that a selection of cells with the L. timidus X-chromosome had taken place, but the degree of this selection was not great enough to allow any of the lesions to be defined as monoclonal.