Turnover of apoE in normal and hypercholesterolemic rats

The turnover of apoE in the total lipoprotein fraction (p less than 1.21 g/ml) of normolipemic and hypercholesterolemic rats was compared. The specific activity of 125I-labelled apoE in the lipoproteins was determined after isolation of the apoprotein by immunoaffinity chromatography. The serum apoE decay curves showed rapid first and slower second phases. The first phase of the curve of hypercholesterolemic animals suggests some sequestration of the apoprotein. The half-lives of apoE in the second phase were approximately 7 and 23 h in the normal and hypercholesterolemic sera, respectively. Elevated apoE levels and moderate hypercholesterolemia persisted one week after restoration of the normal diet, indicating that the increased apoprotein level seen in hypercholesterolemic rats was not solely to VLDL or chylomicron remnants. However, 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.