Use of 3H-cholesteryl linoleyl ether for the quantitation of plasma cholesteryl ester influx into the aortic wall in hypercholesterolemic rabbits.

Abstract

In this study use was made of 3H-cholesteryl linoleyl ether CLE), a nondegradable analogue of cholesteryl ester (CE) to measure plasma lipoprotein CE influx into rabbit aorta. Autologous serum labeled with 3H-CLE was injected into seven hypercholesterolemic rabbits, and more than 90% of the label was recovered in the plasma compartment 10 minutes after injection. Between 4 hours and 3 days the label was cleared from the circulation with a t1/2 of about 24 hours. Between 4 and 24 hours the lipoproteins isolated at d less than 1.006, d less than 1.019, and d less than 1.063 approached similar specific activity, assuming that 3H-CLE had mixed with the lipoprotein CE pool. The rabbits were killed 7 to 14 days after injection when plasma radioactivity decreased to less than 0.03% of injected dose/ml. Total recovery of the CLE ranged from 70% to 95% and 48% to 72% were found in the liver. The minimum influx of plasma CE into the aortic intima was determined by dividing the label found in the artery by the mean specific activity of the labeled compound in the plasma. The minimum influx into regions with atheromatous involvement ranged from 0.8 to 3.4 micrograms CE/cm2/hr. The rate of influx was highly correlated with the amount of CE mass in the intima and media indicating that the bulk of aortic CE is derived from plasma lipoprotein CE. The method described might be useful in distinguishing between possible effects of "antiatherogenic" drugs on plasma CE influx into the aortic wall from an effect on intracellular CE hydrolysis and subsequent efflux of free cholesterol from the artery.