Histopathology of arterial lesions in LPA transgenic mice on cholesterol-enriched chow.

The aortic root from 21 LPA transgenic mice and 18 control litter mates on cholesterol enriched chow were studied histologically for the presence of atherosclerotic lesions. Serial sections were cut and the total area of the lesions was measured by use of computerised image analysis. Lipid staining lesions were found in 17 aortas of the transgenic mice and were five times more common than in the controls. Foam cell lesions were the only type of lesion in 12 of the aortas from transgenic animals, while five animals had developed fibrofatty lesions. Immunostaining revealed monocytes/macrophages on the endothelial surface, and in the subendothelial space of foam cell lesions. In fibrofatty lesions, spindle shaped cells formed a cap around the lipid core. This study supports the view that transgenic mice expressing human apolipoprotein (a) on a high fat and cholesterol diet, are more susceptible to aortic lesions than control mice and develop early atherosclerotic lesions comparable to lesions in man. Aminoguanidin in the drinking water had no effect on the aortic lesions, but lesion size was significantly, negatively correlated with plasma glucose concentration.