Arteriosclerosis and Thrombosis, Vol 12, 237-249, Copyright © 1992 by American Heart Association

ARTICLES

Lipoprotein-proteoglycan complexes from atherosclerotic lesions promote cholesteryl ester accumulation in human monocytes/macrophages

P Vijayagopal, SR Srinivasan, B Radhakrishnamurthy and GS Berenson
Department of Medicine, Lousiana State University Medical Center, New Orleans 70112.

Lipoprotein-proteoglycan complexes from human atherosclerotic lesions were studied to determine their ability to stimulate cholesteryl ester accumulation in human monocytes/macrophages. Complexes containing apolipoprotein (apo) B lipoproteins and proteoglycans were extracted from fatty streaks and fibrous plaque lesions of human aortas by extraction with 0.15 M NaCl. Fractionation of the complex with Bio-Gel A-50m yielded a single fraction from fatty streaks and two fractions from fibrous plaques. The complexes were further purified by anti-apo B affinity chromatography and analyzed for apolipoproteins, lipids, and glycosaminoglycans Apo B was the only apolipoprotein present in the complexes. Although the complexes from fatty streaks and fibrous plaques contained varying proportions of hyaluronic acid, chondroitin 6- sulfate, and dermatan sulfate, heparin was present in only the fibrous plaque complexes. All three lipoprotein-proteoglycan complexes increased the rate of incorporation of [14C]oleate into cholesteryl [14C]oleate and stimulated cholesteryl ester accumulation in monocytes/macrophages. However, the complexes from fibrous plaques were more potent than those from fatty streaks in this regard. Cholesteryl ester synthesis that is mediated by the uptake of the complexes was dose dependent and showed apparent saturation, suggesting that cell surface binding may be required. Chloroquine, a lysosomotropic agent, inhibited cholesteryl ester synthesis that is induced by the complexes, indicating that lysosomal hydrolysis was essential. Cholesteryl ester synthesis that is mediated by the complexes was inhibited 70-79% by polyinosinic acid. Furthermore, excess unlabeled fibrous plaque complexes significantly inhibited the binding and internalization of in vitro 125I-low density lipoprotein (LDL)-proteoglycan complexes and 125I-acetylated-LDL and not 125I-LDL. These results suggest the involvement of the scavenger receptor in the uptake of the complexes. Phagocytosis played a minor role in the metabolism of these ligands because cytochalasin D inhibited cholesteryl ester synthesis, which is mediated by fibrous plaque complexes, by 7.5-25%. Cholesteryl ester synthesis increased linearly over 32 hours in macrophages incubated with the complexes, indicating an apparent lack of downregulation of binding sites. This resulted in the appearance of intracellular oil red O-positive lipid droplets. These studies show for the first time that apo B lipoprotein-proteoglycan complexes isolated from human atherosclerotic lesions can induce cholesteryl ester accumulation in monocytes/macrophages.

This article has been cited by other articles:

				R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]

				M. Kaplan and M. Aviram Retention of Oxidized LDL by Extracellular Matrix Proteoglycans Leads to Its Uptake by Macrophages : An Alternative Approach to Study Lipoproteins Cellular Uptake Arterioscler Thromb Vasc Biol, March 1, 2001; 21(3): 386 - 393. [Abstract] [Full Text] [PDF]

				D. C. Schwenke Metabolic evidence for sequestration of low-density lipoprotein in abdominal aorta of normal rabbits Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1128 - H1140. [Abstract] [Full Text] [PDF]

				U. Lundstam, E. Hurt-Camejo, G. Olsson, P. Sartipy, G. Camejo, and O. Wiklund Proteoglycans Contribution to Association of Lp(a) and LDL With Smooth Muscle Cell Extracellular Matrix Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1162 - 1167. [Abstract] [Full Text] [PDF]

				K. Oorni, J. K. Hakala, A. Annila, M. Ala-Korpela, and P. T. Kovanen Sphingomyelinase Induces Aggregation and Fusion, but Phospholipase A2 Only Aggregation, of Low Density Lipoprotein (LDL) Particles. TWO DISTINCT MECHANISMS LEADING TO INCREASED BINDING STRENGTH OF LDL TO HUMAN AORTIC PROTEOGLYCANS J. Biol. Chem., October 30, 1998; 273(44): 29127 - 29134. [Abstract] [Full Text] [PDF]

				A. Daugherty, J. A. Cornicelli, K. Welch, S. M. Sendobry, and D. L. Rateri Scavenger Receptors are Present on Rabbit Aortic Endothelial Cells In Vivo Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2369 - 2375. [Abstract] [Full Text]

				J. M. Manning, I. J. Edwards, W. D. Wagner, J. D. Wagner, M. R. Adams, and J. S. Parks Effects of Contraceptive Estrogen and Progestin on the Atherogenic Potential of Plasma LDLs in Cynomolgus Monkeys Arterioscler Thromb Vasc Biol, July 1, 1997; 17(7): 1216 - 1223. [Abstract] [Full Text]

				Y. Shi, J. E. O'Brien Jr, J. D. Mannion, R. C. Morrison, W. Chung, A. Fard, and A. Zalewski Remodeling of Autologous Saphenous Vein Grafts : The Role of Perivascular Myofibroblasts Circulation, June 17, 1997; 95(12): 2684 - 2693. [Abstract] [Full Text]

				E. Hurt-Camejo, U. Olsson, O. Wiklund, G. Bondjers, and G. Camejo Cellular Consequences of the Association of ApoB Lipoproteins With Proteoglycans: Potential Contribution to Atherogenesis Arterioscler Thromb Vasc Biol, June 1, 1997; 17(6): 1011 - 1017. [Abstract] [Full Text]

				P. Vijayagopal and D. L. Glancy Macrophages Stimulate Cholesteryl Ester Accumulation in Cocultured Smooth Muscle Cells Incubated With Lipoprotein-Proteoglycan Complex Arterioscler Thromb Vasc Biol, September 1, 1996; 16(9): 1112 - 1121. [Abstract] [Full Text]

				Y. Wang, K. A. Lindstedt, and P. T. Kovanen Mast Cell Granule Remnants Carry LDL Into Smooth Muscle Cells of the Synthetic Phenotype and Induce Their Conversion Into Foam Cells Arterioscler Thromb Vasc Biol, June 1, 1995; 15(6): 801 - 810. [Abstract] [Full Text]

				K. Paananen, J. Saarinen, A. Annila, and P. T. Kovanen Proteolysis and Fusion of Low Density Lipoprotein Particles Strengthen Their Binding to Human Aortic Proteoglycans J. Biol. Chem., May 19, 1995; 270(20): 12257 - 12262. [Abstract] [Full Text] [PDF]

				K. J. Williams and I. Tabas The Response-to-Retention Hypothesis of Early Atherogenesis Arterioscler Thromb Vasc Biol, May 1, 1995; 15(5): 551 - 561. [Full Text]