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.
P Vijayagopal, S R Srinivasan, J H Xu, E R Dalferes Jr, B Radhakrishnamurthy, G S Berenson
Title and authors | Publication | Year |
---|---|---|
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Hyperelongated biglycan: the surreptitious initiator of atherosclerosis
PJ Little, N Osman, KD OʼBrien |
Current Opinion in Lipidology | 2008 |
Fatty acid-induced atherogenic changes in extracellular matrix proteoglycans
M Rodriguéz-Lee, G Bondjers, G Camejo |
Current Opinion in Lipidology | 2007 |
Hyaluronan forms complexes with low density lipoprotein while also inducing foam cell infiltration in the dermis
M Seike, M Ikeda, M Matsumoto, R Hamada, M Takeya, H Kodama |
Journal of Dermatological Science | 2006 |
Macrophage-released proteoglycans enhance LDL aggregation: studies in aorta from apolipoprotein E-deficient mice
I Maor, T Hayek, M Hirsh, TC Iancu, M Aviram |
Atherosclerosis | 2000 |
Metabolic evidence for sequestration of low-density lipoprotein in abdominal aorta of normal rabbits
DC Schwenke |
American journal of physiology. Heart and circulatory physiology | 2000 |
Lipoprotein lipase-mediated interactions of small proteoglycans and low-density lipoproteins
E Schönherr, B Zhao, H Hausser, M Müller, C Langer, WD Wagner, IJ Goldberg, H Kresse |
European Journal of Cell Biology | 2000 |
Vascular biology, atherosclerosis, and implications for cardiac care
GS Berenson, SR Srinivasan, B Radhakrishnamurthy |
Current Atherosclerosis Reports | 1999 |
Serum Amyloid A, an Acute-Phase Protein, Modulates Proteoglycan Synthesis in Cultured Murine Peritoneal Macrophages
R Elliott-Bryant, JE Silbert, G Sugumaran |
Biochemical and Biophysical Research Communications | 1999 |
Enhanced macrophage uptake of lipoprotein(a) after Ca2+-induced aggregate-formation
S Tanaka, A Yashiro, H Tasaki, Y Nakashima |
Lipids | 1998 |
Association of apo B lipoproteins with arterial proteoglycans: Pathological significance and molecular basis
G Camejo, E Hurt-Camejo, O Wiklund, G Bondjers |
Atherosclerosis | 1998 |
Distribution of Hyaluronan and Dermatan/Chondroitin Sulfate Proteoglycans in Human Aortic Dissection
PS Gutierrez, MM Reis, ML Higuchi, VD Aiello, NA Stolf, EA Lopes |
Connective Tissue Research | 1998 |
Proteoglycans in macrophages: characterization and possible role in the cellular uptake of lipoproteins
B Halvorsen, UK Aas, MA Kulseth, CA Drevon, EN Christiansen, SO Kolset |
Biochemical Journal | 1998 |
Antioxidants and atherogenesis
DC Schwenke |
The Journal of Nutritional Biochemistry | 1998 |
Comparison of Apolipoprotein and Proteoglycan Deposits in Human Coronary Atherosclerotic Plaques: Colocalization of Biglycan With Apolipoproteins
KD OBrien, KL Olin, CE Alpers, W Chiu, M Ferguson, K Hudkins, TN Wight, A Chait |
Circulation | 1998 |
The heparin-bound fraction of human lipoprotein-deficient serum inhibits endocytic uptake of oxidized low density lipoprotein by macrophages
Y Suginohara, A Miyazaki, H Hakamata, YI Sakamoto, T Ohta, I Matsuda, S Horiuchi |
Atherosclerosis | 1996 |
Lipoprotein lipase stimulates the binding and uptake of moderately oxidized low-density lipoprotein by J774 macrophages
WL Hendriks, H der Boom, LC van Vark, LM Havekes |
Biochemical Journal | 1996 |
Antioxidants, dietary fat saturation, lipoprotein oxidation and atherogenesis
DC Schwenke |
Nutrition | 1996 |
Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis
IJ Goldberg |
Journal of lipid research | 1996 |
Development of the Lipid-Rich Core in Human Atherosclerosis
JR Guyton, KF Klemp |
Arteriosclerosis, thrombosis, and vascular biology | 1996 |
Apolipoproteins B, (a), and E Accumulate in the Morphologically Early Lesion of ‘Degenerative’ Valvular Aortic Stenosis
KD OBrien, DD Reichenbach, SM Marcovina, J Kuusisto, CE Alpers, CM Otto |
Arteriosclerosis, thrombosis, and vascular biology | 1996 |
Macrophages Stimulate Cholesteryl Ester Accumulation in Cocultured Smooth Muscle Cells Incubated With Lipoprotein-Proteoglycan Complex
P Vijayagopal, DL Glancy |
Arteriosclerosis, thrombosis, and vascular biology | 1996 |
Regulation of the metabolism of lipoprotein-proteoglycan complexes in human monocyte-derived macrophages
P Vijayagopal |
Biochemical Journal | 1994 |
The biology of the artery wall in atherogenesis
KD O'Brien, A Chait |
Medical Clinics of North America | 1994 |
Oxidation of heparin-isolated LDL by hemin. The effect of serum components
WH Sutherland |
Arteriosclerosis Thrombosis and Vascular Biology | 1994 |