Influx of [3H,14C]cholesterol-labelled lipoprotein into re-endothelialized and de-endothelialized areas of ballooned aortas in normal-fed and cholesterol-fed rabbits

Abstract

The entry of [3H]- and [3H,14C]cholesterol-labelled lipoprotein into de-endothelialized and re-endothelialized areas of balloon-injured rabbit aortas was studied in normal-fed and cholesterol-fed rabbits. Studies were carried out 11-15 weeks after the initial injury when endothelial regeneration involved approximately half of the aortic area. The entry into the aorta of 3H-labelled free and ester cholesterol in lipoprotein over a 72-h period was studied following the ingestion of a single dose of 3H-labelled cholesterol. The entry of double labelled [3H,14C]cholesterol-labelled lipoprotein was also studied over a 6-h period following the injection of plasma from donor rabbits. The accumulation of cholesterol and cholesterol ester in the aorta in both the normal- and cholesterol-fed rabbits was significantly greater for the re-endothelialized (white) areas than for the de-endothelialized (blue) areas or the sham-operated aortas. Where the rabbits were cholesterol-fed 4-10 times the amount of cholesterol accumulated in re-endothelialized intima compared to normal intima. Both entry (micrograms/day/100 mg wet weight aortic intima) and clearance (mu 1 plasma/day/cm2) of free and ester cholesterol were increased in the neointima compared with the normal intima for both normal-fed and cholesterol-fed rabbits. Hydrolysis of cholesterol ester occurred in the neointima and was greater than in the corresponding de-endothelialized area but less than for the sham-operated intima. Synthesis of cholesterol ester was minimal in all areas. Removal of labelled cholesterol and cholesterol ester from the intima during a 20-h efflux period following the initial 72-h loading period indicated that for aortas of both normal-fed and cholesterol-fed rabbits, there was greater removal for normal intima than for either re-endothelialized or de-endothelialized intima. However, no clear difference between the blue and white areas was observed. It is concluded that the accumulation of cholesterol in neointima after balloon injury is associated with a marked increase in permeability to lipoprotein of the neointima as well as to possible binding of lipoprotein to glycosaminoglycan in the artery.