HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Dijk, K. W. Articles by Hofker, M. H. Search for Related Content PubMed PubMed Citation Articles by van Dijk, K. W. Articles by Hofker, M. H. Social Bookmarking                      What's this?

The Journal of Lipid Research, Vol. 40, 336-344, February 1999
Copyright © 1999 by Lipid Research, Inc.

Original Article

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

Correspondence to: Ko Willems van Dijk

To investigate the quantitative requirement for apolipoprotein (apo) E in the clearance of lipoproteins via the non-low density lipoprotein (LDL) receptor mediated pathway, human APOE was overexpressed at various levels in the livers of mice deficient for both the endogenous Apoe and Ldlr genes (Apoe -/- · Ldlr -/-) using adenovirus-mediated gene transfer. We found that a low level of APOE expression, that was capable of reducing the hyperlipidemia in Apoe -/- mice, did not result in a reduction of the hyperlipidemia in Apoe -/- · Ldlr -/- mice. Surpisingly, a very high level of APOE expression also did not result in a reduction of hypercholesterolemia in Apoe -/- · Ldlr -/- mice, despite very high levels of circulating apoE (>160 mg/dl). Only a moderately high level of APOE expression resulted in a reduction of serum cholesterol level (from 35.2 ± 6.7 to 14.6 ± 2.3 mmol/l) and the disappearance of VLDL from the serum. Moreover, the very high level of APOE expression resulted in a severe hypertriglyceridemia in Apoe -/- · Ldlr -/- mice and not Apoe -/- mice (25.7 ± 8.9 and 2.2 ± 1.8 mmol/l, respectively). This hypertriglyceridemia was associated with an APOE-induced increase in the VLDL triglyceride production rate and an inhibition of VLDL-triglyceride lipolysis.

We conclude from these data that, for efficient clearance, the non-LDL receptor-mediated pathway requires a higher level of APOE expression as compared to the LDL receptor, but is more sensitive to an APOE-induced increase in VLDL production and inhibition of VLDL-triglyceride lipolysis.—van Dijk, K. W., B. J. M. Van Vlijmen, H. B. van't Hof, A. van der Zee, S. Santamarina-Fojo, T. J. C. van Berkel, L. M. Havekes, and M. H. Hofker. In LDL receptor-deficient mice, catabolism of remnant lipoproteins requires a high level of apoE but is inhibited by excess APOE. J. Lipid Res. 1999. 40: 336–344.

Supplementary key words: adenovirus-mediated gene transfer, LDL receptor-related protein, hypertriglyceridemia, VLDL-triglyceride lipolysis, hepatic VLDL triglyceride production

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. Gerritsen, C. C. van der Hoogt, F. G. Schaap, P. J. Voshol, K. E. Kypreos, N. Maeda, A. K. Groen, L. M. Havekes, P. C. N. Rensen, and K. W. van Dijk ApoE2-associated hypertriglyceridemia is ameliorated by increased levels of apoA-V but unaffected by apoC-III deficiency J. Lipid Res., May 1, 2008; 49(5): 1048 - 1055. [Abstract] [Full Text] [PDF]

				B. Loeffler, J. Heeren, M. Blaeser, H. Radner, D. Kayser, B. Aydin, and M. Merkel Lipoprotein lipase-facilitated uptake of LDL is mediated by the LDL receptor J. Lipid Res., February 1, 2007; 48(2): 288 - 298. [Abstract] [Full Text] [PDF]

				G. Gerritsen, P. C. N. Rensen, K. E. Kypreos, V. I. Zannis, L. M. Havekes, and K. Willems van Dijk ApoC-III deficiency prevents hyperlipidemia induced by apoE overexpression J. Lipid Res., July 1, 2005; 46(7): 1466 - 1473. [Abstract] [Full Text] [PDF]

				S. M. S. Espirito Santo, N. M. M. Pires, L. S. M. Boesten, G. Gerritsen, N. Bovenschen, K. W. van Dijk, J. W. Jukema, H. M. G. Princen, A. Bensadoun, W.-P. Li, et al. Hepatic low-density lipoprotein receptor-related protein deficiency in mice increases atherosclerosis independent of plasma cholesterol Blood, May 15, 2004; 103(10): 3777 - 3782. [Abstract] [Full Text] [PDF]

				G. Gerritsen, K. E. Kypreos, A. van der Zee, B. Teusink, V. I. Zannis, L. M. Havekes, and K. W. van Dijk Hyperlipidemia in APOE2 transgenic mice is ameliorated by a truncated apoE variant lacking the C-terminal domain J. Lipid Res., February 1, 2003; 44(2): 408 - 414. [Abstract] [Full Text] [PDF]

				M. E. Hinsdale, P. M. Sullivan, H. Mezdour, and N. Maeda ApoB-48 and apoB-100 differentially influence the expression of type-III hyperlipoproteinemia in APOE*2 mice J. Lipid Res., September 1, 2002; 43(9): 1520 - 1528. [Abstract] [Full Text] [PDF]

				M.-a. Kawashiri, Y. Zhang, D. Usher, M. Reilly, E. Puré, and D. J. Rader Effects of coexpression of the LDL receptor and apoE on cholesterol metabolism and atherosclerosis in LDL receptor-deficient mice J. Lipid Res., June 1, 2001; 42(6): 943 - 950. [Abstract] [Full Text]

				K. C-W. Yu, Y. Jiang, W. Chen, and A. D. Cooper Rapid initial removal of chylomicron remnants by the mouse liver does not require hepatically localized apolipoprotein E J. Lipid Res., November 1, 2000; 41(11): 1715 - 1727. [Abstract] [Full Text]

				F. de Beer, K. W. van Dijk, M. C. Jong, L. C. van Vark, A. van der Zee, M. H. Hofker, F. J. Fallaux, R. C. Hoeben, A. H. M. Smelt, and L. M. Havekes Apolipoprotein E2 (Lys146->Gln) Causes Hypertriglyceridemia due to an Apolipoprotein E Variant-Specific Inhibition of Lipolysis of Very Low Density Lipoproteins-Triglycerides Arterioscler. Thromb. Vasc. Biol., July 1, 2000; 20(7): 1800 - 1806. [Abstract] [Full Text] [PDF]

				P. C. N. Rensen, M. C. Jong, L. C. van Vark, H. van der Boom, W. L. Hendriks, T. J. C. van Berkel, E. A. L. Biessen, and L. M. Havekes Apolipoprotein E Is Resistant to Intracellular Degradation in Vitro and in Vivo. EVIDENCE FOR RETROENDOCYTOSIS J. Biol. Chem., March 17, 2000; 275(12): 8564 - 8571. [Abstract] [Full Text] [PDF]

				A. R Mensenkamp, M. C Jong, H. van Goor, M. J. A. van Luyn, V. Bloks, R. Havinga, P. J. Voshol, M. H. Hofker, K. W. van Dijk, L. M. Havekes, et al. Apolipoprotein E Participates in the Regulation of Very Low Density Lipoprotein-Triglyceride Secretion by the Liver J. Biol. Chem., December 10, 1999; 274(50): 35711 - 35718. [Abstract] [Full Text] [PDF]

				B. J. M. van Vlijmen, A. Rohlmann, S. T. Page, A. Bensadoun, I. S. T. Bos, T. J. C. van Berkel, L. M. Havekes, and J. Herz An Extrahepatic Receptor-associated Protein-sensitive Mechanism Is Involved in the Metabolism of Triglyceride-rich Lipoproteins J. Biol. Chem., December 3, 1999; 274(49): 35219 - 35226. [Abstract] [Full Text] [PDF]

				K. W. van Dijk, B. J.M. van Vlijmen, M. P.J. de Winther, B. van ’t Hof, A. van der Zee, H. van der Boom, L. M. Havekes, and M. H. Hofker Hyperlipidemia of ApoE2(Arg158-Cys) and ApoE3-Leiden Transgenic Mice Is Modulated Predominantly by LDL Receptor Expression Arterioscler. Thromb. Vasc. Biol., December 1, 1999; 19(12): 2945 - 2951. [Abstract] [Full Text] [PDF]

				R. W. Mahley, Y. Huang, and S. C. Rall , Jr. Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia): questions, quandaries, and paradoxes J. Lipid Res., November 1, 1999; 40(11): 1933 - 1949. [Abstract] [Full Text]

				R. K. Tangirala, D. Pratico, G. A. FitzGerald, S. Chun, K. Tsukamoto, C. Maugeais, D. C. Usher, E. Pure, and D. J. Rader Reduction of Isoprostanes and Regression of Advanced Atherosclerosis by Apolipoprotein E J. Biol. Chem., January 5, 2001; 276(1): 261 - 266. [Abstract] [Full Text] [PDF]

				C. Knouff, S. Malloy, J. Wilder, M. K. Altenburg, and N. Maeda Doubling Expression of the Low Density Lipoprotein Receptor by Truncation of the 3'-Untranslated Region Sequence Ameliorates Type III Hyperlipoproteinemia in Mice Expressing the Human ApoE2 Isoform J. Biol. Chem., February 2, 2001; 276(6): 3856 - 3862. [Abstract] [Full Text] [PDF]