Effects of moderate hypercholesterolemia on rabbit endothelium.

We investigated the effects of moderate hypercholesterolemia and endothelial regrowth on the function of vascular endothelium. Groups of rabbits were fed either a high or low cholesterol diet and subjected to removal of the aortic endothelium or sham-operated. Endothelial removal caused diffuse thickening of the myointima. The high cholesterol diet did not affect the extent of endothelial regeneration. To test endothelial function, 1 minute before sacrifice each animal was infused with horseradish peroxidase, which will penetrate the intima in areas of increased permeability. After sacrifice, the aorta was removed en bloc and exposed to diaminobenzidine and H2O2, which produce a brown stain on reaction with horseradish peroxidase. The luminal surface of the aorta was examined, and brown-stained areas, indicating increased permeability, were quantitated by stereology. Rabbits fed the cholesterol-rich diet had a greater percentage of brown-stained areas than did rabbits fed the low cholesterol diet; this was true for both intact and regenerated endothelium. The differences were significant at the p less than 0.01 level. Scanning electron microscopy of brown areas showed that, although the surface characteristics of the endothelium were altered, endothelial sloughing did not occur. Therefore, it appears that hypercholesterolemia can be associated with a functional endothelial defect in the absence of endothelial loss.