TURNOVER OF APOE IN NORMAL AND HYPERCHOLESTEROLEMIC RATS

Abstract

The turnover of apoE in the total lipoprotein fraction (.rho. [density] < 1.21 g/ml) of normolipemic and hypercholesterolemic rats was compared. The specific activity of 125I-labeled apoE in the lipoproteins was determined after isolation of the apoprotein by immunoaffinity chromatography. The serum apoE decay curves showed rapid 1st and slower 2nd phases. The 1st phase of the curve of hypercholesterolemic animals suggests some sequestration of the apoprotein. The half-lives of apoE in the 2nd phase were .apprx. 7 and 23 h in the normal and hypercholesterolemic sera, respectively. Elevated apoE levels and a moderate hypercholesterolemia persisted 1 wk after restoration of the normal diet, indicating that the increased apoprotein level seen in hypercholesterolemic rats was not due solely to VLDL [very low density lipoprotein] or chylomicron remnants. Due to the elevated apoE levels in the hypercholesterolemic rats, the total replacement rates of the apoprotein appeared to be greater than that in normolipemic animals, consistent with the concept that in the steady state there is an increase in apoE secretion in hypercholesterolemic animals rather than a decrease in catabolism.