Uptake and degradation of low density lipoproteins in atherosclerotic rabbit aorta: role of local LDL modification.
The uptake of native and modified low density lipoprotein (LDL) in foam cells in atherosclerotic tissue was studied in an in vitro perfusion system for rabbit aorta. Experimental atherosclerosis was induced in rabbits by a combination of cholesterol feeding and mechanical injury. The aorta was perfused in an incubation chamber. A trace-label, radioiodinated tyramine-cellobiose, was used to study cellular uptake of lipoproteins. After perfusion, the tissue was digested and cells were isolated by centrifugation in a density gradient. About 40 times more LDL per cell was accumulated in the foam cell fraction than in the smooth muscle cell fraction. When the cellular uptake of LDL and acetylated LDL (AcLDL) was compared, about 4 times more AcLDL than LDL was taken up by the foam cells, suggesting that the scavenger receptor is expressed in these cells. In a competition experiment, the uptake of LDL into foam cells was reduced by 70% when a tenfold excess of AcLDL was added. This experiment suggests that native LDL is taken up by the same mechanism as AcLDL. The accumulation of radiolabeled LDL in plaques and in foam cells was reduced by 30-55% by adding vitamin E (0.1 mg/ml) to the system. These studies show an uptake of LDL by foam cells in the atherosclerotic tissue. Furthermore, these cells seem to express the scavenger receptor. The competition experiment would suggest that native LDL is taken up by the scavenger receptor. The observation that an antioxidant, vitamin E, may decrease this uptake suggests that oxidative modification of LDL is of importance for this process.
Wiklund
O
O
Wallenberg Laboratory for Cardiovascular Research, Department of Medicine I, University of Gothenburg, Sweden.
Mattsson
L
L
Björnheden
T
T
Camejo
G
G
Bondjers
G
G
D000107:Acetylation; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism*; D001667:Binding, Competitive; D002469:Cell Separation; D002499:Centrifugation, Density Gradient; D005487:Foam Cells / Q000378:metabolism; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010477:Perfusion; D011817:Rabbits; D014810:Vitamin E / Q000494:pharmacology
D008077:Lipoproteins, LDL; D014810:Vitamin E