Lipoprotein-proteoglycan complexes induce continued cholesteryl ester accumulation in foam cells from rabbit atherosclerotic lesions.
We studied the metabolism of lipoprotein-proteoglycan complexes by macrophage-derived foam cells. Foam cells were isolated from atherosclerotic rabbit aortas. ApoB-lipoprotein-proteoglycan complex was isolated from human aorta fibrous plaque lesions and LDL-proteoglycan complex was formed in vitro. Both in vitro and in vivo complexes stimulated cholesteryl ester synthesis in foam cells by a dose-dependent, saturable process that resulted in the intracellular accumulation of cholesteryl ester. Stimulation of cholesteryl ester synthesis was linear with time over a 32-h period. Polyinosinic acid inhibited the stimulation of cholesteryl ester synthesis by the complexes by 32-37%, whereas cytochalasin D only produced a 6-16% inhibition. Foam cells degraded 125I-LDL-proteoglycan complex and 125I-acetyl LDL in a saturable, dose-dependent manner. Excess unlabeled acetyl-LDL inhibited the degradation of 125I-LDL-proteoglycan complex by 52%, while LDL had no effect. Similarly, excess unlabeled complex suppressed the degradation of 125I-acetyl-LDL by 48%. Foam cells degraded 125I-methyl-LDL-proteoglycan complex to the same extent as 125I-LDL-proteoglycan complex. These results show that foam cells from atherosclerotic lesions metabolize lipoprotein-proteoglycan complexes predominantly via receptor-mediated endocytosis and consequently continue to accumulate intracellular cholesteryl ester.
Vijayagopal
P
P
Department of Medicine, Louisiana State University Medical Center, New Orleans 70112.
Srinivasan
S R
SR
Xu
J H
JH
Dalferes
E R
ER
Radhakrishnamurthy
B
B
Berenson
G S
GS
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D002791:Cholesterol, Dietary; D002809:Chondroitin Sulfates / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000494:pharmacology; D004036:Diet, Atherogenic; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007083:Iliac Artery / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011069:Poly I / Q000494:pharmacology; D011509:Proteoglycans / Q000494:pharmacology*; D011817:Rabbits
D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D015638:Cytochalasin D; D003871:Dermatan Sulfate; D011069:Poly I; D002809:Chondroitin Sulfates; D002784:Cholesterol