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

Abstract

The entry of [ 3H]- and [ 3H, 14C]cholesterol-labelled lipoprotein into de-endothelialised and re-endothelialised 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 dinor 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-endothelialised (white) areas than for the de-endothelialised (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 (μg/day/100 mg wet weight aortic intima) and clearance (μl plasma/ day/cm 2) 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-endothelialised 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-endothelialised or de-endothelialised 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.