In LDL receptor-deficient mice, catabolism of remnant lipoproteins requires a high level of apoE but is inhibited by excess apoE

Journal of Lipid Research

Volumn 40, Issue 2, 1999, Pages 336-344

  Van Dijk, Ko Willems ^a   Van Vlijmen, Bart J M ^b,c   Van't Hof, H Belinda ^c   Van Der Zee, Andre ^a   Santamarina Fojo, Silvia ^d   Van Berkel, Theo J C ^b   Havekes, Louis M ^a,c   Hofker, Marten H ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^b LEIDEN UNIVERSITY   (Netherlands)

^c TNO   (Netherlands)

^d NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

Adenovirus mediated gene transfer; Hepatic VLDL triglyceride production; Hypertriglyceridemia; LDL receptor related protein; VLDL triglyceride lipolysis

Indexed keywords

APOLIPOPROTEIN E; CHOLESTEROL; LIPOPROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR; TRIACYLGLYCEROL; VERY LOW DENSITY LIPOPROTEIN; LIPOPROTEIN LIPASE; VERY LOW DENSITY LIPOPROTEIN TRIGLYCERIDE;

ADENOVIRUS; ANIMAL MODEL; ARTICLE; CATABOLISM; CONTROLLED STUDY; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; GENE; GENE TRANSFER; HUMAN; HYPERTRIGLYCERIDEMIA; IMMUNOHISTOCHEMISTRY; LIPOLYSIS; LIVER; MICROSCOPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; ANIMAL; BIOSYNTHESIS; BLOOD; GENETIC TRANSFECTION; GENETICS; METABOLISM; TRANSGENIC MOUSE;

ADENOVIRIDAE; ANIMALS; APOLIPOPROTEINS E; CHOLESTEROL; FEMALE; HUMANS; IMMUNOHISTOCHEMISTRY; LIPOLYSIS; LIPOPROTEIN LIPASE; LIPOPROTEINS; LIPOPROTEINS, VLDL; LIVER; MICE; MICE, TRANSGENIC; RECEPTORS, LDL; TRANSFECTION; TRIGLYCERIDES;

EID: 0032946723     PISSN: 00222275     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (47)

1. Mahley, R. W. 1988. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 240: 622-630.
2. Mahley, R. W., and S. C. Rall, Jr. 1989. Type III hyperlipoproteinemia (dysbetalipoproteinemia): the role of apolipoprotein E in normal and abnormal lipoprotein metabolism. In The Metabolic Basis of Inherited Disease. 6th ed. Chapter 47. C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle, editors. McGraw-Hill, New York. 1195-1213.
3. Rall, S. C., Jr., and R. W. Mahley. 1992. The role of apolipoprotein E genetic variants in lipoprotein disorders. J. Intern. Med. 231: 653-659.
4. Plump, A. S., J. D. Smith, T. Hayek, K. Aalto-Setala, A. Walsh, J. G. Verstuyft, E. M. Rubin, and J. L. Breslow. 1992. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell. 71: 343-353.
5. Zhang, S. H., R. L. Reddick, J. A. Piedrahita, and N. Maeda. 1992. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science. 258: 468-471.
6. van Ree, J. H., W. J. van den Broek, V. E. Dahlmans, P. H. Groot, M. Vidgeon Hart, R. R. Frants, B. Wieringa, L. M. Havekes, and M. H. Hofker. 1994. Diet-induced hypercholesterolemia and atherosclerosis in heterozygous apolipoprotein E-deficient mice. Athrosclerosis. 111:25-37.
7. Ishibashi, S., S. Perrey, Z. Chen, J. Osuga, M. Shimada, K. Ohashi, K. Harada, Y. Yazaki, and N. Yamada. 1996. Role of the low density lipoprotein (LDL) receptor pathway in the metabolism of chylomicron remnants. A quantitative study in knockout mice lacking the LDL receptor, apolipoprotein E, or both. J. Biol. Chem. 271: 22422-22427.
8. Windler, E. E., J. Greeve, W. H. Daerr, and H. Greten. 1988. Binding of rat chylomicrons and their remnants to the hepatic low-density-lipoprotein receptor and its role in remnant removal. Biochem. J. 252:553-561.
9. Choi, S. Y., L. G. Fong, M. J. Kirven, and A. D. Cooper. 1991. Use of an anti-low density lipoprotein receptor antibody to quantify the role of the LDL receptor in the removal of chylomicron remnants in the mouse in vivo. J. Clin. Invest. 88: 1173-1181.
10. Mahley, R. W., and M. M. Hussain. 1991. Chylomicron and chylomicron remnant metabolism. Curr. Opin. Lipidol. 2: 170-176.
11. Ishibashi, S., J. Herz, N. Maeda, J. L. Goldstein, and M. S. Brown. 1994. The two-receptor model of lipoprotein clearance: tests of the hypothesis in "knockout" mice lacking the low density lipoprotein receptor, apolipoprotein E, or both proteins. Proc. Natl. Acad. Sci. USA. 91: 4431-4435.
12. Herz, J., and T. E. Willnow. 1995. Lipoprotein and receptor interactions in vivo. Curr. Opin. Lipidol. 6: 97-103.
13. Beisiegel, U., A. Krapp, W. Weber, and G. Olivecrona. 1994. The role of alpha 2M receptor/LRP in chylomicron remnant metabolism. Ann. NY Acad. Sci. 737: 53-69.
14. Herz, J., J. L. Goldstein, D. K. Strickland, Y. K. Ho, and M. S. Brown. 1991. 39-kDa protein modulates binding of ligands to low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. J. Biol. Chem. 266: 21232-21238.
15. Willnow, T. E., Z. Sheng, S. Ishibashi, and J. Herz. 1994. Inhibition of hepatic chylomicron remnant uptake by gene transfer of a receptor antagonist. Science. 264: 1471-1474.
16. Rohlmann, A., M. Gotthardt, R. E. Hammer, and J. Herz. 1998. Inducible inactivation of hepatic LRP gene by Cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants. J. Clin. Invest. 101: 689-695.
17. Ji, Z. S., W. J. Brecht, R. D. Miranda, M. M. Hussain, T. L. Innerarity, and R. W. Mahley. 1993. Role of heparan sulfate proteoglycans in the binding and uptake of apolipoprotein E-enriched remnant lipoproteins by cultured cells. J. Biol. Chem. 268: 10160-10167.
18. van Dijk, M. C., J. K. Kruijt, W. Boers, C. Linthorst, and T. J. van Berkel. 1992. Distinct properties of the recognition sites for beta-very low density lipoprotein (remnant receptor) and alpha 2-macroglobulin (low density lipoprotein receptor-related protein) on rat parenchymal cells. J. Biol. Chem. 267: 17732-17737.
19. Yen, F. T., C. J. Mann, L. M. Guermani, N. F. Hannouche, N. Hubert, C. A. Hornick, V. N. Bordeau, G. Agnani, and B. E. Bihain. 1994. Identification of a lipolysis-stimulated receptor that is distinct from the LDL receptor and the LDL receptor-related protein. Biochemistry 33: 1172-1180.
20. Windler, E., J. Greeve, S. Jackle, F. Rinninger, C. Pox, D. Puchta, D. Petkova, H. Robenek, W. Daerr, and H. Greten. 1996. Endocytic mechanisms for uptake and metabolism of chylomicron remnants in the liver. Z. Gastroenterol. 34 Suppl. 3: 103-104.
21. Rensen, P. C., N. Herijger, M. H. Netscher, M. C. Meskers, M. van Eck, and T. J. van Berkel. 1997. Particle size determines the specificity of apolipoprotein E-containing triglyceride-rich emulsions for the LDL receptor versus the hepatic remnant receptor in vivo. J. Lipid Res. 38: 1070-1084.
22. Kowal, R. C., J. Herz, K. H. Weisgraber, R. W. Mahley, M. S. Brown, and J. L. Goldstein. 1990. Opposing effects of apolipoproteins E and C on lipoprotein binding to low density lipoprotein receptor-related protein. J. Biol. Chem. 265: 10771-10779.
23. Hussain, M. M., F. R. Maxfield, J. Mas Oliva, I. Tabas, Z. S. Ji, T. L. Innerarity, and R. W. Mahley. 1991. Clearance of chylomicron remnants by the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor. J. Biol. Chem. 266: 13936-13940.
24. Shimano, H., Y. Namba, J. Ohsuga, M. Kawamura, K. Yamamoto, M. Shimada, T. Gotoda, K. Harada, Y. Yazaki, and N. Yamada. 1994. Secretion-recapture process of apolipoprotein E in hepatic uptake of chylomicron remnants in transgenic mice. J. Clin. Invest. 93: 2215-2223.
25. Ji, Z. S., S. Fazio, Y. L. Lee, and R. W. Mahley. 1994. Secretion-capture role for apolipoprotein E in remnant lipoprotein metabolism involving cell surface heparan sulfate proteoglycans. J. Biol. Chem. 269: 2762-2772.
26. Ishibashi, S., M. S. Brown, J. L. Goldstein, R. D. Gerard, R. E. Hammer, and J. Herz. 1993. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery [see Comments]. J. Clin. Invest. 92: 883-893.
27. Kashyap, V. S., S. Santamarina-Fojo, D. R. Brown, C. L. Parrott, D. Applebaum-Bowden, S. Meyn, G. Talley, B. Paigen, N. Maeda, and H. B. Brewer, Jr. 1995. Apolipoprotein E deficiency in mice: gene replacement and prevention of atherosclerosis using adenovirus vectors. J. Clin. Invest. 96: 1612-1620.
28. Fallaux, F. J., O. Kranenburg, S. J. Cramer, A. Houweling, H. Van Ormondt, R. C. Hoeben, and A. J. Van Der Eb. 1996. Characterization of 911: a new helper cell line for the titration and propagation of early region 1-deleted adenoviral vectors. Hum. Gene Ther. 7: 215-222.
29. Redgrave, T. G., D. C. Roberts, and C. E. West. 1975. Separation of plasma lipoproteins by density-gradient ultracentrifugation. Anal. Biochem. 65: 42-49.
30. van Vlijinen, B. J., H. B. van't Hof, M. J. Mol, H. van der Boom, A. van der Zee, R. R. Frants, M. H. Hofker, and L. M. Havekes. 1996. Modulation of very low density lipoprotein production and clearance contributes to age- and gender-dependent hyperlipoproteinemia in apolipoprotein E3-Leiden transgenic mice. J. Clin. Invest. 97: 1184-1192.
31. Lowry, O. H., N. J. Rosebrough, A. L. Farr, and R. J. Randall. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 265-275.
32. Otway, S., and D. S. Robinson. 1967. The use of a non-ionic detergent (Triton WR 1339) to determine rates of triglyceride entry into the circulation of the rat under different physiological conditions. J. Physiol. London. 190: 321-332.
33. van Vlijmen, B. J., K. W. van Dijk, H. B. van't Hof, P. J. van Gorp, A. van der Zee, H. van der Boom, M. L. Breuer, M. H. Hofker, and L. M. Havekes. 1996. In the absence of endogenous mouse apolipoprotein E, apolipoprotein E*2(Arg-158→Cys) transgenic mice develop more severe hyperlipoproteinemia than apolipoprotein E*3-Leiden transgenic mice. J. Biol. Chem. 271: 30595-30602.
34. Jong, M. C., V. E. Dahlmans, P. J. van Gorp, K. W. van Dijk, M. L. Breuer, M. H. Hofker, and L. M. Havekes. 1996. In the absence of the low density lipoprotein receptor, human apolipoprotein C-I overexpression in transgenic mice inhibits the hepatic uptake of very low density lipoprotein via a receptor-associated protein-sensitive pathway. J. Clin. Invest. 98: 2259-2267.
35. Medh, J. D., G. L. Fry, S. L. Bowen, M. W. Pladet, D. K. Strickland, and D. A. Chappell. 1995. The 39-kDa receptor-associated protein modulates lipoprotein catabolism by binding to LDL receptors. J. Biol. Chem. 270: 536-540.
36. Herz, J., S. Q. Qiu, A. Oesterle, H. V. DeSilva, S. Shafi, and R. J. Havel. 1995. Initial hepatic removal of chylomicron remnants is unaffected but endocytosis is delayed in mice lacking the low density lipoprotein receptor. Proc. Natl. Acad. Sci. USA. 92: 4611-4615.
37. Kuipers, F., M. C. Jong, Y. Lin, M. van Eck, R. Havinga, V. Bloks, H. J. Verkade, M. H. Hofker, H. Moshage, T. J. C. van Berkel, R. J. Vonk, and L. M. Havekes. 1997. Impaired production of very low density lipoprotein-triglycerides by apolipoprotein E-deficient mouse hepatocytes. J. Clin. Invest. 100: 2915-2922.
38. Mulder, M., H. van der Boom, P. de Knijff, C. Braam, A. van den Maagdenberg, J. A. Leuven, and L. M. Havekes. 1994. Triglyceride-rich lipoproteins of subjects heterozygous for apolipoprotein E2(Lys146→Gln) are inefficiently converted to cholesterol-rich lipoproteins. Atherosclerosis. 108: 183-192.
39. Jong, M. C., V. E. Dahlmans, P. J. van Gorp, M. L. Breuer, M. J. Mol, A. van der Zee, R. R. Frants, M. H. Hofker, and L. M. Havekes. 1996. Both lipolysis and hepatic uptake of VLDL are impaired in transgenic mice coexpressing human apolipoprotein E*3Leiden and human apolipoprotein C-I. Arterioscler. Thromb. Vasc. Biol. 16: 934-940.
40. Huang Y., X. Q. Liu, S. C. Rall, Jr., and R. W. Mahley. 1998. Apolipoprotein E2 reduces the low density lipoprotein level in transgenic mice by impairing lipoprotein lipase-mediated lipolysis of triglyceride-rich lipoproteins. J. Biol. Chem. 273: 17483-17490.
41. Rensen, P. C. N., and T. J. C. van Berkel. 1996. Apolipoprotein E effectively inhibits lipoprotein lipase-mediated lipolysis of chylomicron-like triglyceride-rich lipid emulsions in vitro and in vivo. J. Biol. Chem. 271: 14791-14799.
42. Gomez Coronado, D., G. T. Saez, M. A. Lasuncion, and E. Herrera. 1993. Different hydrolytic efficiencies of adipose tissue lipoprotein lipase on very-low-density lipoprotein subtractions separated by heparin-Sepharose chromatography. Biochim. Biophys. Acta. 1167: 70-78.
43. Jong, M. C., V. E. Dahlmans, M. H. Hofker, and L. M. Havekes. 1997. Nascent very-low-density lipoprotein triacylglycerol hydrolysis by lipoprotein lipase is inhibited by apolipoprotein E in a dose-dependent manner. Biochem. J. 328: 745-750.
44. Havel, R. J., C. J. Fielding, T. Olivecrona, V. G. Shore, P. E. Fielding, and T. Egelrud. 1973. Cofactor activity of protein components of human very low density lipoproteins in the hydrolysis of triglycerides by lipoproteins lipase from different sources. Biochemistry. 12: 1828-1833.
45. LaRosa, J. C., R. I. Levy, P. Herbert, S. E. Lux, and D. S. Fredrickson. 1970. A specific apoprotein activator for lipoprotein lipase. Biochem. Biophys. Res Commun. 41: 57-62.
46. Huang Y., S. W. Schwendner, and S. C. Rall, Jr., and R. W. Mahley. 1996. Hypolipidemic and hyperlipidemic phenotypes in transgenic mice expressing human apolipoprotein E2. J. Biol. Chem. 271: 29146-29151.
47. Huang Y., S. C. Rall Jr., and R. W. Mahley. 1997. Genetic factors precipitating type III hyperlipoproteinemia in hypolipidemic transgenic mice expressing human apolipoprotein E2. Arterioscler. Thromb. Vasc. Biol. 17: 2817-2824.