Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Oct;88(4):1300–1306. doi: 10.1172/JCI115434

Lipoprotein lipase modulates net secretory output of apolipoprotein B in vitro. A possible pathophysiologic explanation for familial combined hyperlipidemia.

K J Williams 1, K A Petrie 1, R W Brocia 1, T L Swenson 1
PMCID: PMC295599  PMID: 1918380

Abstract

We showed previously that net secretory output of apolipoprotein B (apo B) from cultured human hepatoma cells (HepG2) is regulated by rapid reuptake of nascent lipoproteins before they have diffused away from the vicinity of the cells. We now sought to determine if the nascent lipoproteins could be remodeled to enhance or impede reuptake. We found that lipoprotein lipase (LpL), an enzyme that hydrolyzes lipoprotein triglyceride, reduced HepG2 output of apo B to one-quarter to one-half of control. The reduction was apparent during co-incubations as short as 2 h and as long as 24 h. Heparin, which blocks receptor-mediated binding of lipoproteins, abolished the effect of LpL on apo B output, without causing enzyme inhibition. To assess uptake directly, we prepared labeled nascent lipoproteins. LpL tripled the cellular uptake of labeled nascent lipoproteins, from 15.2% +/- 0.7% to 48.7% +/- 0.3% of the total applied to the cells. Cellular uptake of 125I-labeled anti-LDL receptor IgG was unaffected by LpL; thus, LpL enhanced reuptake by altering lipoproteins, not receptors. Because LpL is present in the space of Disse in the liver, we conclude that LpL may act on newly secreted lipoproteins to enhance reuptake in vivo. LpL deficiency would reduce local reuptake of apo B, which would appear as overproduction, thereby providing a mechanistic link between partial LpL deficiency and familial combined hyperlipidemia.

Full text

PDF
1300

Selected References

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

  1. Arad Y., Ramakrishnan R., Ginsberg H. N. Lovastatin therapy reduces low density lipoprotein apoB levels in subjects with combined hyperlipidemia by reducing the production of apoB-containing lipoproteins: implications for the pathophysiology of apoB production. J Lipid Res. 1990 Apr;31(4):567–582. [PubMed] [Google Scholar]
  2. Ashwell G., Morell A. G. The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv Enzymol Relat Areas Mol Biol. 1974;41(0):99–128. doi: 10.1002/9780470122860.ch3. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. 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]
  6. Baker D. P., Van Lenten B. J., Fogelman A. M., Edwards P. A., Kean C., Berliner J. A. LDL, scavenger, and beta-VLDL receptors on aortic endothelial cells. Arteriosclerosis. 1984 May-Jun;4(3):248–255. doi: 10.1161/01.atv.4.3.248. [DOI] [PubMed] [Google Scholar]
  7. Beisiegel U., Schneider W. J., Goldstein J. L., Anderson R. G., Brown M. S. Monoclonal antibodies to the low density lipoprotein receptor as probes for study of receptor-mediated endocytosis and the genetics of familial hypercholesterolemia. J Biol Chem. 1981 Nov 25;256(22):11923–11931. [PubMed] [Google Scholar]
  8. Belfrage P., Vaughan M. Simple liquid-liquid partition system for isolation of labeled oleic acid from mixtures with glycerides. J Lipid Res. 1969 May;10(3):341–344. [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. Bisgaier C. L., Siebenkas M. V., Brown M. L., Inazu A., Koizumi J., Mabuchi H., Tall A. R. Familial cholesteryl ester transfer protein deficiency is associated with triglyceride-rich low density lipoproteins containing cholesteryl esters of probable intracellular origin. J Lipid Res. 1991 Jan;32(1):21–33. [PubMed] [Google Scholar]
  11. Bisgaier C. L., Siebenkas M. V., Williams K. J. Effects of apolipoproteins A-IV and A-I on the uptake of phospholipid liposomes by hepatocytes. J Biol Chem. 1989 Jan 15;264(2):862–866. [PubMed] [Google Scholar]
  12. Borensztajn J., Getz G. S., Kotlar T. J. Uptake of chylomicron remnants by the liver: further evidence for the modulating role of phospholipids. J Lipid Res. 1988 Aug;29(8):1087–1096. [PubMed] [Google Scholar]
  13. Borensztajn J., Kotlar T. J., McNeill B. J. Uptake of phospholipid-depleted chylomicrons by the perfused rat liver. Biochem J. 1980 Dec 15;192(3):845–851. doi: 10.1042/bj1920845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Burgaya F., Peinado J., Vilaró S., Llobera M., Ramírez I. Lipoprotein lipase activity in neonatal-rat liver cell types. Biochem J. 1989 Apr 1;259(1):159–166. doi: 10.1042/bj2590159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Catapano A. L., Gianturco S. H., Kinnunen P. K., Eisenberg S., Gotto A. M., Jr, Smith L. C. Suppression of 3-hydroxy-3-methylglutaryl-CoA reductase by low density lipoproteins produced in vitro by lipoprotein lipase action on nonsuppressive very low density lipoproteins. J Biol Chem. 1979 Feb 25;254(4):1007–1009. [PubMed] [Google Scholar]
  16. Chait A., Iverius P. H., Brunzell J. D. Lipoprotein lipase secretion by human monocyte-derived macrophages. J Clin Invest. 1982 Feb;69(2):490–493. doi: 10.1172/JCI110473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Egusa G., Brady D. W., Grundy S. M., Howard B. V. Isopropanol precipitation method for the determination of apolipoprotein B specific activity and plasma concentrations during metabolic studies of very low density lipoprotein and low density lipoprotein apolipoprotein B. J Lipid Res. 1983 Sep;24(9):1261–1267. [PubMed] [Google Scholar]
  18. Eisenberg S., Friedman G., Vogel T. Enhanced metabolism of normolipidemic human plasma very low density lipoprotein in cultured cells by exogenous apolipoprotein E-3. Arteriosclerosis. 1988 Sep-Oct;8(5):480–487. doi: 10.1161/01.atv.8.5.480. [DOI] [PubMed] [Google Scholar]
  19. Ellsworth J. L., Erickson S. K., Cooper A. D. Very low and low density lipoprotein synthesis and secretion by the human hepatoma cell line Hep-G2: effects of free fatty acid. J Lipid Res. 1986 Aug;27(8):858–874. [PubMed] [Google Scholar]
  20. Fisher E. A., Coates P. M., Cortner J. A. Gene polymorphisms and variability of human apolipoproteins. Annu Rev Nutr. 1989;9:139–160. doi: 10.1146/annurev.nu.09.070189.001035. [DOI] [PubMed] [Google Scholar]
  21. Fuki I. V., Preobrazhensky S. N., Misharin AYu, Bushmakina N. G., Menschikov G. B., Repin V. S., Karpov R. S. Effect of cell cholesterol content on apolipoprotein B secretion and LDL receptor activity in the human hepatoma cell line, HepG2. Biochim Biophys Acta. 1989 Feb 6;1001(2):235–238. doi: 10.1016/0005-2760(89)90153-7. [DOI] [PubMed] [Google Scholar]
  22. Goldberg I. J., Scheraldi C. A., Yacoub L. K., Saxena U., Bisgaier C. L. Lipoprotein ApoC-II activation of lipoprotein lipase. Modulation by apolipoprotein A-IV. J Biol Chem. 1990 Mar 15;265(8):4266–4272. [PubMed] [Google Scholar]
  23. 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]
  24. Goldstein J. L., Basu S. K., Brunschede G. Y., Brown M. S. Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans. Cell. 1976 Jan;7(1):85–95. doi: 10.1016/0092-8674(76)90258-0. [DOI] [PubMed] [Google Scholar]
  25. Gottlieb B. A., Marsh J. B. High density lipoprotein binding by rat Fu5AH hepatoma cells is not related to cholesterol content. Atherosclerosis. 1987 Oct;67(2-3):251–259. doi: 10.1016/0021-9150(87)90286-3. [DOI] [PubMed] [Google Scholar]
  26. Grundy S. M., Vega G. L. Fibric acids: effects on lipids and lipoprotein metabolism. Am J Med. 1987 Nov 27;83(5B):9–20. doi: 10.1016/0002-9343(87)90866-7. [DOI] [PubMed] [Google Scholar]
  27. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Hamilton R. L., Regen D. M., Gray M. E., LeQuire V. S. Lipid transport in liver. I. Electron microscopic identification of very low density lipoproteins in perfused rat liver. Lab Invest. 1967 Feb;16(2):305–319. [PubMed] [Google Scholar]
  29. Handlogten M. E., Weissbach L., Kilberg M. S. Heterogeneity of Na+-independent 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid and L-leucine transport in isolated rat hepatocytes in primary culture. Biochem Biophys Res Commun. 1982 Jan 15;104(1):307–313. doi: 10.1016/0006-291x(82)91975-1. [DOI] [PubMed] [Google Scholar]
  30. Harrison J. C., Swift L. L., LeQuire V. S. Identification of lipoprotein-binding proteins in rat liver Golgi apparatus membranes. J Lipid Res. 1988 Nov;29(11):1439–1449. [PubMed] [Google Scholar]
  31. Hayden M. R., Kirk H., Clark C., Frohlich J., Rabkin S., McLeod R., Hewitt J. DNA polymorphisms in and around the Apo-A1-CIII genes and genetic hyperlipidemias. Am J Hum Genet. 1987 May;40(5):421–430. [PMC free article] [PubMed] [Google Scholar]
  32. Hui D. Y., Innerarity T. L., Mahley R. W. Defective hepatic lipoprotein receptor binding of beta-very low density lipoproteins from type III hyperlipoproteinemic patients. Importance of apolipoprotein E. J Biol Chem. 1984 Jan 25;259(2):860–869. [PubMed] [Google Scholar]
  33. Ishibashi S., Yamada N., Shimano H., Mori N., Mokuno H., Gotohda T., Kawakami M., Murase T., Takaku F. Apolipoprotein E and lipoprotein lipase secreted from human monocyte-derived macrophages modulate very low density lipoprotein uptake. J Biol Chem. 1990 Feb 25;265(6):3040–3047. [PubMed] [Google Scholar]
  34. Jackson R. L., Tajima S., Yamamura T., Yokoyama S., Yamamoto A. Comparison of apolipoprotein C-II-deficient triacylglycerol-rich lipoproteins and trioleoylglycerol/phosphatidylcholine-stabilized particles as substrates for lipoprotein lipase. Biochim Biophys Acta. 1986 Feb 12;875(2):211–219. doi: 10.1016/0005-2760(86)90170-0. [DOI] [PubMed] [Google Scholar]
  35. Jensen G. L., Baly D. L., Brannon P. M., Bensadoun A. Synthesis and secretion of lipolytic enzymes by cultured chicken hepatocytes. J Biol Chem. 1980 Dec 10;255(23):11141–11148. [PubMed] [Google Scholar]
  36. Khoo J. C., Mahoney E. M., Witztum J. L. Secretion of lipoprotein lipase by macrophages in culture. J Biol Chem. 1981 Jul 25;256(14):7105–7108. [PubMed] [Google Scholar]
  37. Kinoshita M., Krul E. S., Schonfeld G. Modification of the core lipids of low density lipoproteins produces selective alterations in the expression of apoB-100 epitopes. J Lipid Res. 1990 Apr;31(4):701–708. [PubMed] [Google Scholar]
  38. Kissebah A. H., Alfarsi S., Adams P. W., Seed M., Folkard J., Wynn V. Transport kinetics of plasma free fatty acid, very low density lipoprotein triglycerides and apoprotein in patients with endogenous hypertriglyceridaemia: effects of 2,2-dimethyl, 5(2, 5-xylyoxy) valeric acid therapy. Atherosclerosis. 1976 Jul-Aug;24(1-2):199–218. doi: 10.1016/0021-9150(76)90076-9. [DOI] [PubMed] [Google Scholar]
  39. Kleinman Y., Krul E. S., Burnes M., Aronson W., Pfleger B., Schonfeld G. Lipolysis of LDL with phospholipase A2 alters the expression of selected apoB-100 epitopes and the interaction of LDL with cells. J Lipid Res. 1988 Jun;29(6):729–743. [PubMed] [Google Scholar]
  40. Knobler H., Chajek-Shaul T., Stein O., Etienne J., Stein Y. Modulation of lipoprotein lipase in the intact rat by cholera toxin--an irreversible agonist of cyclic AMP. Biochim Biophys Acta. 1984 Sep 12;795(2):363–371. doi: 10.1016/0005-2760(84)90087-0. [DOI] [PubMed] [Google Scholar]
  41. Kowal R. C., Herz J., Weisgraber K. H., Mahley R. W., Brown M. S., Goldstein J. L. Opposing effects of apolipoproteins E and C on lipoprotein binding to low density lipoprotein receptor-related protein. J Biol Chem. 1990 Jun 25;265(18):10771–10779. [PubMed] [Google Scholar]
  42. La Belle M., McCall M. R., Krauss R. M., Forte T. M. Unique structural properties of apolipoprotein B in low-density lipoproteins produced by several human hepatoma-derived cell lines. Biochim Biophys Acta. 1990 Oct 1;1046(3):288–293. doi: 10.1016/0005-2760(90)90243-q. [DOI] [PubMed] [Google Scholar]
  43. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  44. Markwell M. A., Haas S. M., Bieber L. L., Tolbert N. E. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem. 1978 Jun 15;87(1):206–210. doi: 10.1016/0003-2697(78)90586-9. [DOI] [PubMed] [Google Scholar]
  45. Masuno H., Tsujita T., Nakanishi H., Yoshida A., Fukunishi R., Okuda H. Lipoprotein lipase-like activity in the liver of mice with Sarcoma 180. J Lipid Res. 1984 May;25(5):419–427. [PubMed] [Google Scholar]
  46. Ostlund-Lindqvist A. M., Gustafson S., Lindqvist P., Witztum J. L., Little J. A. Uptake and degradation of human chylomicrons by macrophages in culture. Role of lipoprotein lipase. Arteriosclerosis. 1983 Sep-Oct;3(5):433–440. doi: 10.1161/01.atv.3.5.433. [DOI] [PubMed] [Google Scholar]
  47. Packard C. J., Clegg R. J., Dominiczak M. H., Lorimer A. R., Shepherd J. Effects of bezafibrate on apolipoprotein B metabolism in type III hyperlipoproteinemic subjects. J Lipid Res. 1986 Sep;27(9):930–938. [PubMed] [Google Scholar]
  48. Pathak R. K., Yokode M., Hammer R. E., Hofmann S. L., Brown M. S., Goldstein J. L., Anderson R. G. Tissue-specific sorting of the human LDL receptor in polarized epithelia of transgenic mice. J Cell Biol. 1990 Aug;111(2):347–359. doi: 10.1083/jcb.111.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Peterson J., Olivecrona T., Bengtsson-Olivecrona G. Distribution of lipoprotein lipase and hepatic lipase between plasma and tissues: effect of hypertriglyceridemia. Biochim Biophys Acta. 1985 Dec 4;837(3):262–270. doi: 10.1016/0005-2760(85)90049-9. [DOI] [PubMed] [Google Scholar]
  50. Petit D., Bonnefis M. T., Rey C., Infante R. Effects of ciprofibrate and fenofibrate on liver lipids and lipoprotein synthesis in normo- and hyperlipidemic rats. Atherosclerosis. 1988 Dec;74(3):215–225. doi: 10.1016/0021-9150(88)90240-7. [DOI] [PubMed] [Google Scholar]
  51. Posner I., Wang C. S., McConathy W. J. The comparative kinetics of soluble and heparin-Sepharose-immobilized bovine lipoprotein lipase. Arch Biochem Biophys. 1983 Oct 1;226(1):306–316. doi: 10.1016/0003-9861(83)90297-7. [DOI] [PubMed] [Google Scholar]
  52. Rinninger F., Pittman R. C. Mechanism of the cholesteryl ester transfer protein-mediated uptake of high density lipoprotein cholesteryl esters by Hep G2 cells. J Biol Chem. 1989 Apr 15;264(11):6111–6118. [PubMed] [Google Scholar]
  53. Saku K., Gartside P. S., Hynd B. A., Kashyap M. L. Mechanism of action of gemfibrozil on lipoprotein metabolism. J Clin Invest. 1985 May;75(5):1702–1712. doi: 10.1172/JCI111879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Schwartz A. L. The hepatic asialoglycoprotein receptor. CRC Crit Rev Biochem. 1984;16(3):207–233. doi: 10.3109/10409238409108716. [DOI] [PubMed] [Google Scholar]
  55. Semenkovich C. F., Chen S. H., Wims M., Luo C. C., Li W. H., Chan L. Lipoprotein lipase and hepatic lipase mRNA tissue specific expression, developmental regulation, and evolution. J Lipid Res. 1989 Mar;30(3):423–431. [PubMed] [Google Scholar]
  56. Semenkovich C. F., Ostlund R. E., Jr, Olson M. O., Yang J. W. A protein partially expressed on the surface of HepG2 cells that binds lipoproteins specifically is nucleolin. Biochemistry. 1990 Oct 16;29(41):9708–9713. doi: 10.1021/bi00493a028. [DOI] [PubMed] [Google Scholar]
  57. Turner P. R., Cortese C., Wootton R., Marenah C., Miller N. E., Lewis B. Plasma apolipoprotein B metabolism in familial type III dysbetalipoproteinaemia. Eur J Clin Invest. 1985 Apr;15(2):100–112. doi: 10.1111/j.1365-2362.1985.tb00152.x. [DOI] [PubMed] [Google Scholar]
  58. Van Driel I. R., Brown M. S., Goldstein J. L. Stoichiometric binding of low density lipoprotein (LDL) and monoclonal antibodies to LDL receptors in a solid phase assay. J Biol Chem. 1989 Jun 5;264(16):9533–9538. [PubMed] [Google Scholar]
  59. Vasile E., Simionescu M., Simionescu N. Visualization of the binding, endocytosis, and transcytosis of low-density lipoprotein in the arterial endothelium in situ. J Cell Biol. 1983 Jun;96(6):1677–1689. doi: 10.1083/jcb.96.6.1677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Vessby B., Lithell H. Interruption of long-term lipid-lowering treatment with bezafibrate in hypertriglyceridaemic patients. Effects on lipoprotein composition, lipase activities and the plasma lipid fatty acid spectrum. Atherosclerosis. 1990 May;82(1-2):137–143. doi: 10.1016/0021-9150(90)90152-9. [DOI] [PubMed] [Google Scholar]
  61. Vilaró S., Ramírez I., Bengtsson-Olivecrona G., Olivecrona T., Llobera M. Lipoprotein lipase in liver. Release by heparin and immunocytochemical localization. Biochim Biophys Acta. 1988 Mar 25;959(2):106–117. doi: 10.1016/0005-2760(88)90021-5. [DOI] [PubMed] [Google Scholar]
  62. Vilaró S., Reina M., Ramírez I., Llobera M. Intralipid administration induces a lipoprotein lipase-like activity in the livers of starved adult rats. Biochem J. 1986 May 15;236(1):273–278. doi: 10.1042/bj2360273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Wallinder L., Bengtsson G., Olivecrona T. Rapid removal to the liver of intravenously injected lipoprotein lipase. Biochim Biophys Acta. 1979 Oct 26;575(1):166–173. doi: 10.1016/0005-2760(79)90142-5. [DOI] [PubMed] [Google Scholar]
  64. 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]
  65. Weisgraber K. H., Mahley R. W., Kowal R. C., Herz J., Goldstein J. L., Brown M. S. Apolipoprotein C-I modulates the interaction of apolipoprotein E with beta-migrating very low density lipoproteins (beta-VLDL) and inhibits binding of beta-VLDL to low density lipoprotein receptor-related protein. J Biol Chem. 1990 Dec 25;265(36):22453–22459. [PubMed] [Google Scholar]
  66. Weisweiler P. Low-dose colestipol plus fenofibrate: effects on plasma lipoproteins, lecithin:cholesterol acyltransferase, and postheparin lipases in familial hypercholesterolemia. Metabolism. 1989 Mar;38(3):271–274. doi: 10.1016/0026-0495(89)90086-3. [DOI] [PubMed] [Google Scholar]
  67. Williams K. J., Brocia R. W., Fisher E. A. The unstirred water layer as a site of control of apolipoprotein B secretion. J Biol Chem. 1990 Oct 5;265(28):16741–16744. [PubMed] [Google Scholar]
  68. Windler E., Havel R. J. Inhibitory effects of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver. J Lipid Res. 1985 May;26(5):556–565. [PubMed] [Google Scholar]
  69. Wojciechowski A. P., Farrall M., Cullen P., Wilson T. M., Bayliss J. D., Farren B., Griffin B. A., Caslake M. J., Packard C. J., Shepherd J. Familial combined hyperlipidaemia linked to the apolipoprotein AI-CII-AIV gene cluster on chromosome 11q23-q24. Nature. 1991 Jan 10;349(6305):161–164. doi: 10.1038/349161a0. [DOI] [PubMed] [Google Scholar]
  70. Yedgar S., Weinstein D. B., Patsch W., Schonfeld G., Casanada F. E., Steinberg D. Viscosity of culture medium as a regulator of synthesis and secretion of very low density lipoproteins by cultured hepatocytes. J Biol Chem. 1982 Mar 10;257(5):2188–2192. [PubMed] [Google Scholar]
  71. Zechner R., Dieplinger H., Roscher A., Kostner G. M. The low-density-lipoprotein pathway of native and chemically modified low-density lipoproteins isolated from plasma incubated in vitro. Biochem J. 1984 Dec 1;224(2):569–576. doi: 10.1042/bj2240569. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES