Journal of Lipid Research, Vol 38, 765-779, Copyright © 1997 by Lipid Research, Inc.

ARTICLES

Heparan sulfate proteoglycans mediate internalization and degradation of beta-VLDL and promote cholesterol accumulation by pigeon macrophages

T Seo and RW St. Clair
Department of Pathology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1072, USA.

Pigeon and rabbit beta-migrating very low density lipoprotein (beta- VLDL) are similar in size and composition, yet rabbit beta-VLDL consistently stimulates greater cholesteryl ester accumulation in pigeon peritoneal macrophages than does pigeon beta-VLDL. The purpose of this study was to determine the mechanism of this difference. Pigeon beta-VLDL bound to both a high and low affinity site while rabbit beta- VLDL bound primarily to a low affinity site. The high affinity site had the characteristics of the LDL receptor. Most rabbit beta-VLDL and some pigeon beta-VLDL bound to the low affinity site that was not down- regulated by cholesterol loading. beta-VLDL binding to the low affinity site and subsequent internalization and degradation were mediated by cell surface heparan sulfate proteoglycans (HSPG). Evidence for this includes inhibition of binding and uptake by chlorate, which prevents sulfation of proteoglycans, and by treatment with heparinase but not chondroitinase ABC. beta-VLDL uptake was stimulated by lipoprotein lipase (LpL) and apolipoprotein E (apoE), both known to bind HSPGs. Uptake and degradation of beta-VLDL were not mediated by the LDL receptor or the alpha(2)MR/LRP. Thus, binding of beta-VLDL to low affinity, high capacity HSPG binding sites on pigeon macrophages appears to directly promote internalization and degradation and is largely responsible for the greater ability of rabbit beta-VLDL to stimulate cholesterol accumulation.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				U. J. Jung, C. Torrejon, A. P Tighe, and R. J Deckelbaum n-3 Fatty acids and cardiovascular disease: mechanisms underlying beneficial effects Am. J. Clinical Nutrition, June 1, 2008; 87(6): 2003S - 2009S. [Abstract] [Full Text] [PDF]

				G. Qiu and J. S. Hill Endothelial lipase enhances low density lipoprotein binding and cell association in THP-1 macrophages Cardiovasc Res, December 1, 2007; 76(3): 528 - 538. [Abstract] [Full Text] [PDF]

				K. Qi, T. Seo, Z. Jiang, Y. A. Carpentier, and R. J. Deckelbaum Triglycerides in Fish Oil Affect the Blood Clearance of Lipid Emulsions Containing Long- and Medium-Chain Triglycerides in Mice J. Nutr., November 1, 2006; 136(11): 2766 - 2772. [Abstract] [Full Text] [PDF]

				M. Vlasak, I. Goesler, and D. Blaas Human Rhinovirus Type 89 Variants Use Heparan Sulfate Proteoglycan for Cell Attachment J. Virol., May 15, 2005; 79(10): 5963 - 5970. [Abstract] [Full Text] [PDF]

				S. Gingis-Velitski, A. Zetser, V. Kaplan, O. Ben-Zaken, E. Cohen, F. Levy-Adam, Y. Bashenko, M. Y. Flugelman, I. Vlodavsky, and N. Ilan Heparanase Uptake Is Mediated by Cell Membrane Heparan Sulfate Proteoglycans J. Biol. Chem., October 15, 2004; 279(42): 44084 - 44092. [Abstract] [Full Text] [PDF]

				I. V. Fuki, N. Blanchard, W. Jin, D. H. L. Marchadier, J. S. Millar, J. M. Glick, and D. J. Rader Endogenously Produced Endothelial Lipase Enhances Binding and Cellular Processing of Plasma Lipoproteins via Heparan Sulfate Proteoglycan-mediated Pathway J. Biol. Chem., September 5, 2003; 278(36): 34331 - 34338. [Abstract] [Full Text] [PDF]

				L. C. Wilsie and R. A. Orlando The Low Density Lipoprotein Receptor-related Protein Complexes with Cell Surface Heparan Sulfate Proteoglycans to Regulate Proteoglycan-mediated Lipoprotein Catabolism J. Biol. Chem., April 25, 2003; 278(18): 15758 - 15764. [Abstract] [Full Text] [PDF]

				D. Goti, Z. Balazs, U. Panzenboeck, A. Hrzenjak, H. Reicher, E. Wagner, R. Zechner, E. Malle, and W. Sattler Effects of Lipoprotein Lipase on Uptake and Transcytosis of Low Density Lipoprotein (LDL) and LDL-associated alpha -Tocopherol in a Porcine in Vitro Blood-Brain Barrier Model J. Biol. Chem., August 2, 2002; 277(32): 28537 - 28544. [Abstract] [Full Text] [PDF]

				N. L. Jones, J. A. Saunders, and R. R. Mallory Intracellular trafficking of pigeon {beta}-very low density lipoprotein and low density lipoprotein at low and high concentrations in pigeon macrophages J. Lipid Res., November 1, 2000; 41(11): 1823 - 1831. [Abstract] [Full Text]

				B. K. Nordskog, J. W. Reagan , Jr., and R. W. St. Clair Sterol synthesis is up-regulated in cholesterol-loaded pigeon macrophages during induction of cholesterol efflux J. Lipid Res., October 1, 1999; 40(10): 1806 - 1817. [Abstract] [Full Text]

				S. Clasper, S. Vekemans, M. Fiore, M. Plebanski, P. Wordsworth, G. David, and D. G. Jackson Inducible Expression of the Cell Surface Heparan Sulfate Proteoglycan Syndecan-2 (Fibroglycan) on Human Activated Macrophages Can Regulate Fibroblast Growth Factor Action J. Biol. Chem., August 20, 1999; 274(34): 24113 - 24123. [Abstract] [Full Text] [PDF]

				H. S. Kruth, W.-Y. Zhang, S. I. Skarlatos, and F.-F. Chao Apolipoprotein B Stimulates Formation of Monocyte-Macrophage Surface-connected Compartments and Mediates Uptake of Low Density Lipoprotein-derived Liposomes into these Compartments J. Biol. Chem., March 12, 1999; 274(11): 7495 - 7500. [Abstract] [Full Text] [PDF]

				F. de Beer, W. L. Hendriks, L. C. van Vark, S. W.A. Kamerling, K. W. van Dijk, M. H. Hofker, A. H.M. Smelt, and L. M. Havekes Binding of ß-VLDL to Heparan Sulfate Proteoglycans Requires Lipoprotein Lipase, Whereas ApoE Only Modulates Binding Affinity Arterioscler. Thromb. Vasc. Biol., March 1, 1999; 19(3): 633 - 637. [Abstract] [Full Text] [PDF]

				N. F. Galeano, M. Al-Haideri, F. Keyserman, S. C. Rumsey, and R. J. Deckelbaum Small dense low density lipoprotein has increased affinity for LDL receptor-independent cell surface binding sites: a potential mechanism for increased atherogenicity J. Lipid Res., June 1, 1998; 39(6): 1263 - 1273. [Abstract] [Full Text]

				I. V. Fuki, R. V. Iozzo, and K. J. Williams Perlecan Heparan Sulfate Proteoglycan. A NOVEL RECEPTOR THAT MEDIATES A DISTINCT PATHWAY FOR LIGAND CATABOLISM J. Biol. Chem., August 11, 2000; 275(33): 25742 - 25750. [Abstract] [Full Text] [PDF]

				T. Seo, M. Al-Haideri, E. Treskova, T. S. Worgall, Y. Kako, I. J. Goldberg, and R. J. Deckelbaum Lipoprotein Lipase-mediated Selective Uptake from Low Density Lipoprotein Requires Cell Surface Proteoglycans and Is Independent of Scavenger Receptor Class B Type 1 J. Biol. Chem., September 22, 2000; 275(39): 30355 - 30362. [Abstract] [Full Text] [PDF]