Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Nov;90(5):2013–2021. doi: 10.1172/JCI116081

Lipoprotein lipase enhances binding of lipoproteins to heparan sulfate on cell surfaces and extracellular matrix.

S Eisenberg 1, E Sehayek 1, T Olivecrona 1, I Vlodavsky 1
PMCID: PMC443265  PMID: 1430223

Abstract

Lipoprotein lipase enhances binding at 4 degrees C of human plasma lipoproteins (chylomicrons, VLDL, intermediate density lipoprotein, LDL, and HDL3) to cultured fibroblasts and hepG-2 cells and to extracellular matrix. Heparinase treatment of cells and matrix reduces the lipoprotein lipase enhanced binding by 90-95%. Lipoprotein lipase causes only a minimal effect on the binding of lipoproteins to heparan sulfate deficient mutant Chinese hamster ovary cells while it promotes binding to wild type cells that is abolished after heparinase treatment. With 125I-LDL, lipoprotein lipase also enhances uptake and proteolytic degradation at 37 degrees C by normal human skin fibroblasts but has no effect in heparinase-treated normal cells or in LDL receptor-negative fibroblasts. These observations prove that lipoprotein lipase causes, predominantly, binding of lipoproteins to heparan sulfate at cell surfaces and in extracellular matrix rather than to receptors. This interaction brings the lipoproteins into close proximity with cell surfaces and may promote metabolic events that occur at the cell surface, including facilitated transfer to cellular receptors.

Full text

PDF
2021

Images in this article

2018Image
on p.2018
2018Image
on p.2018
2018Image
on p.2018
2018Image
on p.2018
2018Image
on p.2018

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnon R., Sehayek E., Vogel T., Eisenberg S. Effects of exogenous apo E-3 and of cholesterol-enriched meals on the cellular metabolism of human chylomicrons and their remnants. Biochim Biophys Acta. 1991 Oct 1;1085(3):336–342. doi: 10.1016/0005-2760(91)90138-8. [DOI] [PubMed] [Google Scholar]
  2. Aviram M., Bierman E. L., Chait A. Modification of low density lipoprotein by lipoprotein lipase or hepatic lipase induces enhanced uptake and cholesterol accumulation in cells. J Biol Chem. 1988 Oct 25;263(30):15416–15422. [PubMed] [Google Scholar]
  3. Aviram M., Lund-Katz S., Phillips M. C., Chait A. The influence of the triglyceride content of low density lipoprotein on the interaction of apolipoprotein B-100 with cells. J Biol Chem. 1988 Nov 15;263(32):16842–16848. [PubMed] [Google Scholar]
  4. Babirak S. P., Iverius P. H., Fujimoto W. Y., Brunzell J. D. Detection and characterization of the heterozygote state for lipoprotein lipase deficiency. Arteriosclerosis. 1989 May-Jun;9(3):326–334. doi: 10.1161/01.atv.9.3.326. [DOI] [PubMed] [Google Scholar]
  5. Bashkin P., Doctrow S., Klagsbrun M., Svahn C. M., Folkman J., Vlodavsky I. Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules. Biochemistry. 1989 Feb 21;28(4):1737–1743. doi: 10.1021/bi00430a047. [DOI] [PubMed] [Google Scholar]
  6. Beisiegel U., Weber W., Bengtsson-Olivecrona G. Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8342–8346. doi: 10.1073/pnas.88.19.8342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bengtsson-Olivecrona G., Olivecrona T. Phospholipase activity of milk lipoprotein lipase. Methods Enzymol. 1991;197:345–356. doi: 10.1016/0076-6879(91)97160-z. [DOI] [PubMed] [Google Scholar]
  8. Bensadoun A. Lipoprotein lipase. Annu Rev Nutr. 1991;11:217–237. doi: 10.1146/annurev.nu.11.070191.001245. [DOI] [PubMed] [Google Scholar]
  9. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  10. Chajek-Shaul T., Friedman G., Bengtsson-Olivecrona G., Vlodavsky I., Bar-Shavit R. Interaction of lipoprotein lipase with subendothelial extracellular matrix. Biochim Biophys Acta. 1990 Feb 6;1042(2):168–175. doi: 10.1016/0005-2760(90)90003-g. [DOI] [PubMed] [Google Scholar]
  11. Clay M. A., Hopkins G. J., Ehnholm C. P., Barter P. J. The rabbit as an animal model of hepatic lipase deficiency. Biochim Biophys Acta. 1989 Apr 3;1002(2):173–181. doi: 10.1016/0005-2760(89)90284-1. [DOI] [PubMed] [Google Scholar]
  12. Deckelbaum R. J., Eisenberg S., Oschry Y., Butbul E., Sharon I., Olivecrona T. Reversible modification of human plasma low density lipoproteins toward triglyceride-rich precursors. A mechanism for losing excess cholesterol esters. J Biol Chem. 1982 Jun 10;257(11):6509–6517. [PubMed] [Google Scholar]
  13. Deckelbaum R. J., Eisenberg S., Oschry Y., Granot E., Sharon I., Bengtsson-Olivecrona G. Conversion of human plasma high density lipoprotein-2 to high density lipoprotein-3. Roles of neutral lipid exchange and triglyceride lipases. J Biol Chem. 1986 Apr 15;261(11):5201–5208. [PubMed] [Google Scholar]
  14. Esko J. D., Rostand K. S., Weinke J. L. Tumor formation dependent on proteoglycan biosynthesis. Science. 1988 Aug 26;241(4869):1092–1096. doi: 10.1126/science.3137658. [DOI] [PubMed] [Google Scholar]
  15. Felts J. M., Itakura H., Crane R. T. The mechanism of assimilation of constituents of chylomicrons, very low density lipoproteins and remnants - a new theory. Biochem Biophys Res Commun. 1975 Oct 27;66(4):1467–1475. doi: 10.1016/0006-291x(75)90524-0. [DOI] [PubMed] [Google Scholar]
  16. Friedman G., Chajek-Shaul T., Stein O., Olivecrona T., Stein Y. The role of lipoprotein lipase in the assimilation of cholesteryl linoleyl ether by cultured cells incubated with labeled chylomicrons. Biochim Biophys Acta. 1981 Oct 23;666(1):156–164. doi: 10.1016/0005-2760(81)90101-6. [DOI] [PubMed] [Google Scholar]
  17. Friedman G., Gavish D., Vogel T., Eisenberg S. Cellular metabolism of human plasma intermediate-density lipoprotein (IDL). Biochim Biophys Acta. 1990 May 1;1044(1):118–126. doi: 10.1016/0005-2760(90)90226-n. [DOI] [PubMed] [Google Scholar]
  18. Gitay-Goren H., Soker S., Vlodavsky I., Neufeld G. The binding of vascular endothelial growth factor to its receptors is dependent on cell surface-associated heparin-like molecules. J Biol Chem. 1992 Mar 25;267(9):6093–6098. [PubMed] [Google Scholar]
  19. Goldstein J. L., Basu S. K., Brown M. S. Receptor-mediated endocytosis of low-density lipoprotein in cultured cells. Methods Enzymol. 1983;98:241–260. doi: 10.1016/0076-6879(83)98152-1. [DOI] [PubMed] [Google Scholar]
  20. Gospodarowicz D., Mescher A. L., Birdwell C. R. Stimulation of corneal endothelial cell proliferations in vitro by fibroblast and epidermal growth factors. Exp Eye Res. 1977 Jul;25(1):75–89. doi: 10.1016/0014-4835(77)90248-2. [DOI] [PubMed] [Google Scholar]
  21. Herz J., Goldstein J. L., Strickland D. K., Ho Y. K., Brown M. S. 39-kDa protein modulates binding of ligands to low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. J Biol Chem. 1991 Nov 5;266(31):21232–21238. [PubMed] [Google Scholar]
  22. Ishai-Michaeli R., Eldor A., Vlodavsky I. Heparanase activity expressed by platelets, neutrophils, and lymphoma cells releases active fibroblast growth factor from extracellular matrix. Cell Regul. 1990 Oct;1(11):833–842. doi: 10.1091/mbc.1.11.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kern P. A., Martin R. A., Carty J., Goldberg I. J., Ong J. M. Identification of lipoprotein lipase immunoreactive protein in pre- and postheparin plasma from normal subjects and patients with type I hyperlipoproteinemia. J Lipid Res. 1990 Jan;31(1):17–26. [PubMed] [Google Scholar]
  24. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  25. Nader H. B., Dietrich C. P., Buonassisi V., Colburn P. Heparin sequences in the heparan sulfate chains of an endothelial cell proteoglycan. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3565–3569. doi: 10.1073/pnas.84.11.3565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Persson B., Jörnvall H., Olivecrona T., Bengtsson-Olivecrona G. Lipoprotein lipases and vitellogenins in relation to the known three-dimensional structure of pancreatic lipase. FEBS Lett. 1991 Aug 19;288(1-2):33–36. doi: 10.1016/0014-5793(91)80997-h. [DOI] [PubMed] [Google Scholar]
  27. Ruoslahti E., Yamaguchi Y. Proteoglycans as modulators of growth factor activities. Cell. 1991 Mar 8;64(5):867–869. doi: 10.1016/0092-8674(91)90308-l. [DOI] [PubMed] [Google Scholar]
  28. Saxena U., Klein M. G., Vanni T. M., Goldberg I. J. Lipoprotein lipase increases low density lipoprotein retention by subendothelial cell matrix. J Clin Invest. 1992 Feb;89(2):373–380. doi: 10.1172/JCI115595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sehayek E., Lewin-Velvert U., Chajek-Shaul T., Eisenberg S. Lipolysis exposes unreactive endogenous apolipoprotein E-3 in human and rat plasma very low density lipoprotein. J Clin Invest. 1991 Aug;88(2):553–560. doi: 10.1172/JCI115339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Stein O., Halperin G., Leitersdorf E., Olivecrona T., Stein Y. Lipoprotein lipase mediated uptake of non-degradable ether analogues of phosphatidylcholine and cholesteryl ester by cultured cells. Biochim Biophys Acta. 1984 Aug 15;795(1):47–59. doi: 10.1016/0005-2760(84)90103-6. [DOI] [PubMed] [Google Scholar]
  31. Stein O., Stein Y., Goodman D. S., Fidge N. H. The metabolism of chylomicron cholesteryl ester in rat liver. A combined radioautographic-electron microscopic and biochemical study. J Cell Biol. 1969 Dec;43(3):410–431. doi: 10.1083/jcb.43.3.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vlodavsky I., Folkman J., Sullivan R., Fridman R., Ishai-Michaeli R., Sasse J., Klagsbrun M. Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2292–2296. doi: 10.1073/pnas.84.8.2292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wallinder L., Peterson J., Olivecrona T., Bengtsson-Olivecrona G. Hepatic and extrahepatic uptake of intravenously injected lipoprotein lipase. Biochim Biophys Acta. 1984 Oct 4;795(3):513–524. doi: 10.1016/0005-2760(84)90181-4. [DOI] [PubMed] [Google Scholar]
  34. Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]
  35. Williams K. J., Petrie K. A., Brocia R. W., Swenson T. L. Lipoprotein lipase modulates net secretory output of apolipoprotein B in vitro. A possible pathophysiologic explanation for familial combined hyperlipidemia. J Clin Invest. 1991 Oct;88(4):1300–1306. doi: 10.1172/JCI115434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yayon A., Klagsbrun M., Esko J. D., Leder P., Ornitz D. M. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell. 1991 Feb 22;64(4):841–848. doi: 10.1016/0092-8674(91)90512-w. [DOI] [PubMed] [Google Scholar]
  37. Ylä-Herttuala S., Lipton B. A., Rosenfeld M. E., Goldberg I. J., Steinberg D., Witztum J. L. Macrophages and smooth muscle cells express lipoprotein lipase in human and rabbit atherosclerotic lesions. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10143–10147. doi: 10.1073/pnas.88.22.10143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zilversmit D. B. Atherogenesis: a postprandial phenomenon. Circulation. 1979 Sep;60(3):473–485. doi: 10.1161/01.cir.60.3.473. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES