Relationship of an abnormal plasma lipoprotein to protection from atherosclerosis in the cholesterol-fed diabetic rabbit.

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Abstract
Alloxan-diabetic rabbits develop a pronounced hypercholesterolemia and hypertriglyceridemia in response to cholesterol feeding. Despite higher levels of plasma cholesterol, these animals have much less atherosclerosis than cholesterol-fed nondiabetics. To determine whether this effect is due to properties of the lipoproteins, we compared chemical, physical, and metabolic characteristics of a very low density lipoprotein (VLDL) fraction (d less than 1.019 g/ml) from the diabetic and nondiabetic cholesterol-fed rabbits. The molar ratio of triglyceride to cholesteryl ester in the particles from diabetic animals ranged from 2:1 to 6:1, and this ratio remained constant in subfractions from individual rabbits. Triglyceride from nondiabetic control animals was a minor component. Differential scanning calorimetry showed a distinct order-disorder phase transition for cholesteryl ester at approximately 42 degrees C in the fractions from control animals, whereas in fractions from most of the diabetics no such transition was observed, indicating that both triglyceride and cholesteryl ester are present in the core of the same particle. The relative amount of apoprotein E in particles from diabetic animals was much less than that of cholesterol-fed controls. The ability of the lipoproteins from both groups to stimulate cholesteryl ester formation in mouse peritoneal macrophages also was tested. Lipoproteins from cholesterol-fed controls stimulated cholesteryl ester formation in a dose-dependent manner, but particles from the diabetic group had little or no effect. The results suggest that the presence of unusual VLDL particles in diabetic cholesterol-fed rabbits is responsible, at least in part, for the reduced incidence of atherosclerosis in this animal model.