Anti-inflammatory drugs in experimental atherosclerosis. 7. Spontaneous atherosclerosis in WHHL rabbits and inhibition by cortisone acetate.

The Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for familial hypercholesterolemia, has a deficiency in low density lipoprotein (LDL) receptor binding and exhibits elevated plasma lipoprotein levels and spontaneous atherosclerosis. Since atherosclerotic plaque formation has a number of features in common with the inflammatory process, we have investigated the effect of dietary supplementation with an anti-inflammatory steroid (cortisone acetate, 5 mg daily for 3 months) on atherosclerosis using the WHHL rabbit as a model. Atherosclerotic plaque formation in cortisone-fed animals was reduced by about 60% compared to control WHHL rabbits. Steroid administration increased circulating cholesterol levels modestly and triglycerides were increased about 6-fold. While very low density lipoprotein (VLDL)-cholesterol was increased, LDL-cholesterol levels were decreased and the particle was more triglyceride-enriched as well as less dense. Steroid-fed animals also exhibited decreased platelet aggregation and increased aortic 15-lipoxygenase activity. The histological observations showed typical fibrous plaques in aortas of both control and cortisone-fed rabbits, with intima thickened by foamy macrophages and subcellular lipoproteinaceous debris covered by a fibrous cap. These findings thus indicate that steroids reduce the rate of plaque initiation or progression but do not significantly change the histological appearance of the lesion.