Skip to main content
SpringerLink
Log in
Book cover

Vascular Endothelium pp 69–128Cite as

Genetic Factors Contributing to Cardiovascular Disease that may affect Endothelial Structure and Function: The Role of Proteins involved in Lipoprotein Transport

  • Chapter

  • 98 Accesses

Part of the book series: NATO ASI Series ((NSSA,volume 281))

Abstract

Lipoproteins are macromolecular complexes of lipids and proteins which originate mainly from the liver and intestine, and are involved in the transport and redistribution of lipids in the body. The plasma lipoproteins are spherical particles with cores of nonpolar neutral lipid consisting of cholesteryl ester and triglycerides and coats of relatively polar materials consisting of phospholipid, free cholesterol, and proteins(1, 2) (Figure 1 A). The plasma lipoproteins have traditionally been grouped in four major lipoprotein classes: chylomicrons, very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL). A lipoprotein class of intermediate density (IDL) found between VLDL, LDL and several subpopulations of VLDL, LDL and HDL have been described. Finally, lipoprotein particles (Lp) with defined lipid and apolipoprotein composition have also been isolated from plasma and the media of cell cultures (3, 4). The protein components of lipoproteins are called apolipoproteins and have been designated apoA-I, apoA-II, apoA-IV, apoB, apoCI, apo CII, apoCIII, apoD, and apoE (5). The lipid, apolipoprotein composition and the properties of the human plasma lipoproteins are shown in Table I.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References in Order of Appearance

  1. Zannis, V.I., Kardassis, D., and Zanni, E.E. 1993. Genetic mutations affecting human lipoproteins, their receptors and their enzymes. Adv. Hum. Genetics (H. Harris and K. Hirschorn, eds.) Plenum Press, NY. Vol. 21, pp. 145–319.

    Google Scholar 

  2. Herbert, P.N., Assmann, G., Gotto, Jr., A.M., and Fredrickson, D.S. 1982. Familial lipoprotein deficiency: Abetalipoproteinemia, hypobetalipoproteinemia, and Tangier disease, in: “The Metabolic Basis of Inherited Disease” ( J.B. Stanbury, J.B. Wyngaarden, D.S. Fredrickson, J.L. Goldstein, M.D. Brown, eds.), McGraw-Hill, New York, pp. 589–651.

    Google Scholar 

  3. Cheung, M.C., and Alberts, J.J. 1984. Characterization of lipoprotein particles isolated by immune-affinity chromatography. J. Biol. Chem. 259:12201–12209.

    PubMed  CAS  Google Scholar 

  4. Dashti, N., Alaupovic, P., Knight–Gibson, C., and Koren, E. 1987. Identification and partial characterization of discrete apolipoprotein B containing particles human hepatoma cell line HepG2. Biochemistry 26: 4837–4846.

    Article  PubMed  CAS  Google Scholar 

  5. Alaupovic, P. 1971. Conceptual development of the classification systems of plasma lipoproteins. In: “Protides of the Biological Fluids” ( H. Peeters, ed.) Pergammon Press, Oxford, pp. 9–20.

    Google Scholar 

  6. Brown, M.S., Herz, J., Kowal, R.C., and Goldstein, J.L. 1991. The low-density lipoprotein receptor-related protein: Double agent or decoy? Curr. Opin. Lipidol. 2: 65–72.

    Google Scholar 

  7. Brown, M.S., and Goldstein, J.L. 1983. Lipoprotein metabolism in the macrophage: Implications for cholesterol deposition in atherosclerosis. Ann. Rev. Biochem. 52: 223–261.

    Google Scholar 

  8. Plump, A.S., Smith, J.D., Hayek, T., Aalto-Setala, K., Walsh, A., Verstuyft, J.D., Rubin, E.M., Breslow, J.L. 1992. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E–deficient mice created by homologous recombination in ES cells. Cell. 71: 343–3 53.

    Google Scholar 

  9. Ito, Y., Azrolan, N., O’Connel, A., Walsh, A., Breslow, J.L. 1990. Hypertriglyceridemia as a result of apoCIII gene expression in transgenic mice. Science. 249: 790–793.

    Article  PubMed  CAS  Google Scholar 

  10. Walsh, A., Ito, Y., Breslow, J.L. 1989. High levels of the human apolipoprotein A-I in transgenic mice result in increased plasma levels of small high density lipoprotein (HDL) particles comparable to human HDL3. J. Biol. Chem. 264: 6488–6494.

    Google Scholar 

  11. Rubin, E.M., Ishida, B.Y., Clift, S.M,. Krauss, R.M. 1991. Expression of human apolipoprotein A-I in transgenic mice results in reduced plasma levels of murine apolipoprotein A-I and the appearance of two new high density lipoprotein size subclasses. Prvc. Natl. Acad. Sci. USA 88:434–438.

    Article  CAS  Google Scholar 

  12. Rubin, E.M., Krauss, R.M., Spangler, E.A., Verstuyft, J.G., Gift, S.M. 1991. Inhibition of early atherogenesis in transgenic mice by human apolipoprotein A-I. Nature 353: 265–26

    Article  PubMed  CAS  Google Scholar 

  13. Castelli, W.P., J.T. Doyle, T. Gordon, C.G. Hames, M.C. Hjortland, S.B. Hulley, A. Kagan, W.J. Zukel. 1977. HDL cholesterol and other lipids in coronary heart disease: The cooperative lipoprotein phenotyping study. Circulation 55: 767–772.

    Google Scholar 

  14. Heiss, G., H. Tyroler. 1982. In: Proceedings of the Workshop on Apolipoprotein Quantification, NIH Publ. No. 83-1266. U.S. Dept. Health and Human Services, NIH, Bethesda, Maryland. 7–24.

    Google Scholar 

  15. Anderson, K.M., Wilson, P.W.F., Odell, P.M., and Kannel, W.B. 1991. An updated coronary risk profile: A statement for health professionals. Circulation 8:356–362.

    Google Scholar 

  16. Zannis, V.I., S.F. Cole, C. Jackson, D.M. Kurnit and S.K. Karathanasis. 1985. Distribution of apoA-I, apoC-II, apoC-III and apoE mRNA in human tissues, time dependent induction of apoE mRNA by cultures of human monocyte-macrophages. Biochemistry 24: 4450–4455.

    Article  PubMed  CAS  Google Scholar 

  17. Fruchart, J.C., and Bard, J.M. 1991. Lipoprotein particle measurement. An alternative approach to classification of lipid disorders. Curr. Opin. Lipidol. 2: 362–366.

    Google Scholar 

  18. Lagrost, L., L. Persegol, C. and P. Gambert. 1994. Influence of apolipoprotein composition of high density lipoprotein particles on cholesteryl ester transfer protein activity. Particles containing various proportions of apolipoproteins A-I and A-II. J. Biol. Chem. 269: 3189–3197.

    Google Scholar 

  19. Vanloo, B., Taveirne, J., Baert, J., Lorent, G., Lins, L., Ruyschaert, J.M., and Rosseneu, M. 1992. LCAT activation properties of apoA-I CNBr fragments and conversion of discoidal complexes into spherical particles. Biochim. Biophys. Acta 1128: 258–266.

    Google Scholar 

  20. Glueck, C. J., P. Gartside, R. W. Fallat, J. Sielski, P.M. Steiner. 1976. Longevity syndromes: Familial hypobeta-and hyperalphalipoproteinemia. J. Lab. Clin. Med. 88: 941–957.

    Google Scholar 

  21. Glueck, C.J., R.W. Fallat, F. Millet, and M.F. Steiner. 1975. Familial hyperalphalipoproteinemia. Arch. Intern. Med. 135:1025–1028.

    Article  PubMed  CAS  Google Scholar 

  22. Patsch, W., J. Kuisk, C. Glueck, and G. Schonfeld. 1981. Lipoproteins in familial hyperalphalipo proteinemia. Arterioscler. 1: 156–161.

    Article  CAS  Google Scholar 

  23. Strittmatter, W.J., Saunders, A.M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G.S., Roses, A.D. 1993. Apolipoprotein E: High avidity binding to p-amyloid and increased frequency of type 4 allele in late onset familial Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 90: 1977–1981.

    Google Scholar 

  24. Brewer, H.B. Jr., T. Fairwell, A. Larue, R. Ronan, A. Houser, T. Bronzert. 1978. The amino acid sequence of human apoA-I, an apoprotein isolated from high density lipoproteins. Biochem. Biophys. Res. Commun. 80: 623–630.

    Google Scholar 

  25. Zannis, V.I., Karathanasis, S.K., Keutmann, H.T., Goldberger, G., and Breslow, J.L. 1983. Intracellular and extracellular processing of human apoA-I. Secreted apoA-I isoprotein 2 is a propeptide. Proc. Natl. Acad. Sci. USA 80:2574–2578.

    Article  PubMed  CAS  Google Scholar 

  26. Gordon, J.I., Sims, H.F., Lentz, S.R., Edelstein, C., Scanu, A.M., and Strauss, A.W. 1983. Proteolytic processing of human preproapolipoprotein A-I. A proposed defect in the conversion of pro A-I to A-I in Tangier’s disease. J. Biol. Chem. 258: 4037–4044.

    Google Scholar 

  27. Barker, W.C., M.O. Dayhoff. 1977. Evolution of lipoproteins deduced from protein sequence data. Comp. Biochem. Physiol. 57:309–315.

    CAS  Google Scholar 

  28. McLachlin, A.D. 1977. Repeated helical pattern in apolipoprotein A-I. Nature 267: 465–466.

    Article  Google Scholar 

  29. Fitch, W.M. 1977. Phylogenies constrained by the crossover process as illustrated by hemoglobins and a thirteen-cycle, eleven-amino-acid repeat in human apolipoprotein A-I. Genetics 86: 623–644.

    PubMed  CAS  Google Scholar 

  30. Karathanasssis S.K., V.I. Zannis, J.L. Breslow. 1983. Isolation and characterization of the human apolipoprotein A-I gene. Proc. Natl. Acad. Sci. USA 80: 6147–6151.

    Google Scholar 

  31. Li, W.H., M. Tanimura, C.C. Luo, S. Datta, L. Chan. 1988. The apolipoprotein multigene family: biosynthesis, structure, structure-function relationships and evolution. J. Lipid Res. 29: 245–271.

    PubMed  CAS  Google Scholar 

  32. Segrest, J.P., R.L. Jackson, J.D. Morrisett, A.M. Gotto Jr. 1974. A molecular theory of lipid-protein interactions in the plasma lipoproteins. FEBSLetters 38: 247–253.

    Article  PubMed  CAS  Google Scholar 

  33. Wilson, C., M.R. Wardell, K.H. Weisgraber, R.W. Mahley, D.A. Agard. 1991. Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E. Science 252: 1817–1822.

    CAS  Google Scholar 

  34. Wardell, M.R., C. Wilson, A. Agard, R.W. Mahley, and K.H. Weisgraber. 1993. Crystal structures of the common apolipoprotein E variants: Insights into functional mechanisms. “NATO ASI Series”. Vol. II, 73: 81–96.

    Google Scholar 

  35. Wilson C., T. Mau, K.H. Weisgraber, M.R. Wardell, R.W. Mahley, D.A. Agard. 1994. Salt bridge relay triggers defective LDL receptor binding by a mutant apolipoprotein. Structure 2: 713–718.

    Article  PubMed  CAS  Google Scholar 

  36. Breiter, D.R., M.R. Kanost, M.M. Benning, G. Wesenberg, J.H. Law, M.A. Wells, I. Rayment, H.M. Holden. 1990. Molecular structure of an apolipoprotein determined at 2.5A resolution. Biochemistry 30:603–60%.

    Google Scholar 

  37. Nolte, R.T., and D. Atkinson. 1992. Conformational analysis of apolipoprotein A-I and E-3 based on primary sequence and circular dichroism. Biophys. J. 63: 1221.

    Google Scholar 

  38. Marcel, Y.L., P.R. Provost, H. Kos, E. Rattai, N. V. Dac, J.C. Fruchart, E. Rassart. 1991. The epitopes of apolipoprotein A-I define distinct structural domains including a mobile middle region. J. Biol. Chem. 266: 3644–3653.

    Google Scholar 

  39. Segrest, J.P., M.K. Jones, H. De Loof, C.G. Brouillette, Y.V. Venkatachalapathi, and G.M. Ananth aramaiah. 1992. The amphipathic helix in the exchangeable apolipoproteins: A review of secondary structure and function. J. Lipid Res. 33: 141–146.

    Google Scholar 

  40. Srinivas, R.V., Y.V. Venkatachalapathi, R. Zheng, R.J. Owens, K.B. Gupta, S.K. Srinivas, G.M. Anan tharamaiah, J.P. Segrest, and R. W. Compans. 1991. Inhibition of virus-induced cell fiision by apolipoprotein A-I and its amphipathic peptide analogs. J. Cell. Biochem. 45: 224–237.

    Google Scholar 

  41. Kroon, D.J., J.P. Kupferberg, E. Kaiser, and F.J. Kezdy. 1978. Mechanism of lipid-protein interaction in lipoproteins: A synthetic peptide:lecithin vesicle model. J. Am. Chem. Soc. 100: 5975–5977.

    Google Scholar 

  42. Sparrow, J.T., and A.M. Gotto Jr. 1980. Phospholipid binding studies with synthetic apolipoprotein fragments. Ann. N.Y. Acad Sei. 348: 187–211.

    Google Scholar 

  43. Skipski, V. 1972. In: “Blood Lipids and Lipoproteins”: Quantitation, Composition and Metabolism. G. J. Nelson, editor. Wiley-Interscience, New York. 471–583.

    Google Scholar 

  44. Scanu, A.M., C. Edelstein, P. Keim. 1975. In: “The Plasma Proteins”, vol. 1,2nd ed. F. W. Putnam, editor. Academic Press, New York. 317–334.

    Google Scholar 

  45. Atkinson, D., D.M. Small. 1986. Recombinant lipoproteins: implications for structure and assembly of native lipoproteins. Ann. Rev. Biophys. Chem. 15:403–456.

    Article  CAS  Google Scholar 

  46. Atkinson, D., G.G. Shipley. 1984. Structural studies of plasma lipoproteins. Brookhaven Symposium in Biology, 32 Neutrons in Biology. Neutron Scattering Analysis for Biological Studies. (P.B. Schoenborn, ed.) Plenum Publ. pp. 211–226.

    Google Scholar 

  47. Atkinson, D., H.M. Smith, J. Dickson, J.P. Austin. 1976. Interaction of apoprotein from porcine high-density lipoprotein with dimyristoyl lecithin. Eur. J. Biochem. 64: 541–547.

    Google Scholar 

  48. Atkinson, D., D.M. Small, G.G. Shipley. 1980. X-ray and neutron scattering studies of plasma lipoproteins. Ann. N.Y.Acad. Sei. 348: 284–288.

    Google Scholar 

  49. Pownall, H.J., J.B. Massey, S.K. Kusscrow, A.M. Gotto Jr. 1979. Kinetics of lipid protein interactions: Effect of cholesterol on the association of human plasma high density lipoprotein A-I with L-a-dimyristoylphosphatidylcholine. Biochemistry 18: 574–579.

    Google Scholar 

  50. Jonas, A., K.E. Kezdy, and J.H. Wald. 1989. Defined apolipoprotein A-I conformations in reconstituted high density lipoprotein discs. J. Biol. Chem. 264: 4818–4824.

    Google Scholar 

  51. Brasseur, R., J. De Meutter, B. Vanloo, E. Goormaghtigh, J.M. Ruysschaert, and M. Rosseneu. 1990. Mode of assembly of amphipathic helical segments in model high-density lipoproteins. Biochem. Biophys. Acta 1043: 245–252.

    Google Scholar 

  52. Anantharamaiah, G.M., C.G. Brouillette, J.A. Engler, H. De Loof, Y.V. Venkatachalaphathi, J. Boogaerts, and J.P. Segrest. 1990. Role of amphiphatic helices in HDL structure/function. In: “Hypercholesterolemia, Hypocholesterolemia, Hypertriglyceridemia”. ( C.L. Malmendier, ed.) Plenum Press, NY.

    Google Scholar 

  53. Jonas, A., J.H. Wald, K.L. Toohill, E.S. Krul, K.E. Kezdy. 1990. Apolipoprotein A-I structure and lipid properties in homogeneous, reconstituted spherical and discoidal high density lipoproteins. J. Biol. Chem. 265: 22123–22129.

    Google Scholar 

  54. Sparks, D.L., M.C. Phillips, and S. Lund-Katz. 1992. The conformation of apolipoprotein A-I in discoidal and spherical recombinant high density lipoprotein particles: £ NMR studies of lysine ionization behavior. J. Biol. Chem. 267: 25830–25838.

    Google Scholar 

  55. Sparks, D.L., S. Lund-Katz, M.C. Phillips. 1992. The charge and structural stability of apolipoprotein A-I in discoidal and spherical recombinant high density lipoprotein particles. J. Biol. Chem. 267:25839–25847.

    PubMed  CAS  Google Scholar 

  56. Curtiss, L.K. and R.S. Smith. 1988. Localization of two epitopes of apolipoprotein A-I that are exposed on human high density lipoproteins using monoclonal antibodies and synthetic peptides. J. Biol. Chem. 263: 13779–13785.

    Google Scholar 

  57. Silverman, S.R., F. Bernini, J.T. Sparrow, A.M. Gotto Jr., and L.C. Smith. 1987. Monoclonal antibodies as probes of high density lipoprotein structure: Identification and localization of a lipid–dependent epitope. Biochemistry 26: 5833–5843.

    Google Scholar 

  58. Collet, X., B. Perret, G. Simard, E. Raffai, and Y.L. Marcel. 1991. Differential effects of lecithin andcholesterol on the immunoreactivity and conformation of apolipoprotein A-I in high density, lipoproteins. J. Biol. Chem. 266: 9145–9152.

    Google Scholar 

  59. Rothblat, G.H., F.H. Mahlberg, W.J. Johnson, and M.C. Phillips. 1992. Apolipoproteins, membrane cholesterol domains, and the regulation of cholesterol efflux. J. Lipid Res. 33: 1091–1097.

    PubMed  CAS  Google Scholar 

  60. Fielding, C.J. 1990. Lecithin:cholesterol acyltransferase. In: “Advances in Cholesterol Research”. M. Esfahani, J. B. Swaney, editors. Telford Press, Philadelphia. 271–314.

    Google Scholar 

  61. Fielding, C.J., V.G. Shore, P.D. Fielding. 1972. A protein cofactor of lecithin:cholesterol acyltransferase. Biochem. Biophys. Res. Commun. 46: 1943–1949.

    Google Scholar 

  62. Soutar, A.K., C.W. Garner, H.N. Baker, J.T. Sparrow, R.L. Jackson, A.M. Gotto, L.C. Smith. 1975. Effect of the human plasma apolipoproteins and phosphatidylcholine acyl donor on the activity of lecithin: cholesterol acyltransferase. Biochemistry 14: 3057–3064.

    Article  PubMed  CAS  Google Scholar 

  63. Fielding, C. J., P.E. Fielding. 1981. Evidence for a lipoprotein carrier in human plasma catalyzing sterol efflux from cultured fibroblasts and its relationship to lecithin: cholesterol acyltransferase. Proc. Natl. Acad. Sei USA 78: 3911–3914.

    Google Scholar 

  64. Doiy, L., C.H. Sloop, L.M. Boquet, R.L. Hamilton, PS. Roheim. 1983. Lecithin:cholesterol acyltransferase-mediated modification of discoidal peripheral lymph high density lipoproteins: possible mechanism of formation of cholesterol-induced high density lipoproteins (HDLc) in cholesterol-fed dogs. Prvc. Natl. Acad. Sci USA 80: 3489–3493.

    Google Scholar 

  65. Nichols, A. 1990. Conversions in the origins and metabolism of human plasma. In: “Advances in Cholesterol Research”. M. Esfahani, J.M. Swaney, editors. Telford Press, New Jersey. 315–365.

    Google Scholar 

  66. Segrest, J.P., H. DeLoof, J.G. Dohlman, C.G. Brouillette, G.M. Anantharamaiah. 1990. Amphipathic helix motif: classes and properties. Proteins 8: 103–117.

    Article  PubMed  CAS  Google Scholar 

  67. Fukushima, D., S. Yokoyama, D.J. Kroon, F.J. Kezdy, E.T. Kaiser. 1980. Chain length-function correlation of amphiphilic peptides. Synthesis and surface properties of a tetratetracontapeptide segment of apolipoprotein A-I. J. Biol. Chem. 255: 10651–10657.

    Google Scholar 

  68. Utermann, G., J. Haas, A. Steinmetz, R. Paetzold, S.C. Rail Jr., K.H. Weisgraber, R.W. Mahley. 1984. Apolipoprotein A-I and Giessen (Prol43-Arg). A mutant that is defective in activating lecithin. cholesterol acyltransferase. Eur. J. Biochem. 144: 325–331.

    Google Scholar 

  69. Roghani, A., and Zannis, V.I. 1988. Alterations of the Gin residues of human proapoAI by in vitro mutagenesis. Characterization of the normal and mutant protein forms. Biochemistry 27: 7428–7435.

    Google Scholar 

  70. Minnich, A., Collet, X., Roghani, A., Cladaras, C., Hamilton, RX., Fielding, C.J., and Zannis, V.I. 1992. Site-directed mutagenesis and structure-function analysis of the human apolipoprotein A-I. J. Biol Chem. 267: 16553–16560.

    PubMed  CAS  Google Scholar 

  71. Sorci-Thomas, M., M. W. Kearns, and J.P. Lee. 1993. Apolipoprotein A-I domains involved in lecithin-cholesterol acyltransferase activation. J. Biol. Chem. 268: 21403–21409.

    Google Scholar 

  72. Redgrave, T.G., D.C.K. Roberts, C.F. West. 1975. Separation of plasma lipoproteins by density gradient ultracentrifugation. Anal Biochem. 65: 42–49.

    Article  PubMed  CAS  Google Scholar 

  73. Rail, S.C. Jr., K.H. Weisgraber, R.W. Mahley, Y. Ogawa, C.J. Fielding, G. Utermann, J. Haas, A. Steinmetz, H.J. Menzel, G. Assman. 1984. Abnormal lecithin:cholesterol acyltransferase activation by a human apolipoprotein A–I variant in which a single lysine residue is deleted. J. Biol Chem. 259: 10063–10070.

    Google Scholar 

  74. Banka, C.L., R.S. Smith, D.J. Bonnet, L.K. Curtiss. 1990. Localization of an apolipoprotein A-I epitope critical for LCAT activation. J. Biol Chem. 266: 23776–23892.

    Google Scholar 

  75. Stein, O., Y. Stein. 1973. The removal of cholesterol from Landschutz ascites cells by high-density apolipoprotein. Biochim. Biophys. Acta 326: 232–244.

    Google Scholar 

  76. Nakai, T., P.S. Otto, D.L. Kennedy, T.F. Whayne Jr. 1976. Rat high density lipoprotein subfraction (HDL3) uptake and catabolism by isolated rat liver parenchymal cells. J. Biol Chem. 251: 4914–4921.

    PubMed  CAS  Google Scholar 

  77. Drevon, C.A., T. Berg, K.R. Norum. 1977. Uptake and degradation of cholesteiyl ester-labeled rat plasma lipoproteins in purified rat hepatocytes and non-parenchymal liver cells. Biochim. Biophys. Acta 487: 122–136.

    Google Scholar 

  78. Ose, L., I. Roken, K.R. Norum, C. A. Drecon, T. Berg. 1981. The binding of high density lipoproteins to isolated rat hepatocytes. Scand. J. Clin. Invest. 41: 63–73.

    Google Scholar 

  79. Miller, N.E., D.B. Weinstein, D. Steinberg. 1977. Binding, internalization and degradation of high density lipoprotein by culture normal human fibroblasts. J. Lipid Res. 18: 438–450.

    PubMed  CAS  Google Scholar 

  80. Kovanen, P.T., W.J. Schneider, G.M. Hillman, J.L. Goldstein, M.S. Brown. 1979. Separate mechanism for the uptake of high and low density lipoprotein by mouse adrenal gland in vivo. J. Biol Chem. 2 54: 5498–5505.

    Google Scholar 

  81. Kovanen, P.T., M.S. Brown, J.L. Goldstein. 1979. Increased binding of low density lipoprotein to liver membranes from rats treated with i-a-ethinyl estradiol. J. Biol Chem. 254: 11367–11373.

    PubMed  CAS  Google Scholar 

  82. Hui, D. Y., T.L. Innerarity, R.W. Mahley. 1981. Lipoprotein binding to canine hepatic membranes. Metabolically distinct apo-E and apo-B,E receptors. J. Biol Chem. 256: 5646–5654.

    Google Scholar 

  83. Chen, Y.D., F.B. Kroemer, G.M. Reaven. 1980. Identification of specific high density lipoprotein-binding sites in rat testis and regulation of binding by human chorionic gonadotropin. J. Biol Chem. 255: 9162–9167.

    PubMed  CAS  Google Scholar 

  84. Rifici, V.A., H.A. Eder. 1984. A hepatocyte receptor for high-density lipoproteins specific for apolipoprotein A-I. J. Biol Chem. 259: 13814–13818.

    PubMed  CAS  Google Scholar 

  85. Fidge, N.H., P.J. Nestel. 1985. Identification of apolipoprotein involved in the interaction of human high density lipoprotein 3 with receptors on cultured cells. J. Biol Chem. 260: 3570–3575.

    PubMed  CAS  Google Scholar 

  86. Hwang, J., K.M. J. Memon. 1985. Binding of apolipoprotein A-I and A-II after recombination with phospholipid vesicles to the high density lipoprotein receptor of luteinized rat ovary. J. Biol Chem. 60: 5660–5668.

    Google Scholar 

  87. Steinmetz, A., R. Barbaras, N. Ghalim, V. Clavey, J.C. Fruchart, G. Ailhaud. 1990. Human apoli poprotein A-I V binds to apolipoprotein A-I/A-II receptor sites and promotes cholesterol efflux from adipose cells. J. Biol Chem. 265: 7859–7863.

    PubMed  CAS  Google Scholar 

  88. Tabas, I., A.R. Tall. 1984. Mechanism of the association of HDL3 with endothelial cells, smooth muscle cells and fibroblasts. J. Biol Chem. 259: 13897–13905.

    PubMed  CAS  Google Scholar 

  89. Biesbroeck, R., M.F. Oram, J.J. Albers, E.L. Bierman. 1983. Specific high-affinity binding of high density lipoproteins to cultured human skin fibroblasts and arterial smooth muscle cells. J. Clin. Invest 71: 525–539.

    Google Scholar 

  90. Slotte, J.R, J. R Oram, E.L. Bierman. 1987. Binding of high density lipoproteins to cell receptors promotes translocation of cholesterol from intracellular membranes to the cell surface. J. Biol. Chem. 262: 12904–12907.

    Google Scholar 

  91. Graham, D.L., J.R Oram. 1987. Identification and characterization of a high density lipoprotein-binding protein in cell membranes by ligand blotting. J. Biol. Chem. 262:7439–7442.

    PubMed  CAS  Google Scholar 

  92. Schmitz, G., G. Assmann, H. Robenek, B. Brennhausen. 1985. Tangier disease: A disorder of intracellular membrane traffic. Proc. Natl. Acad. Sci. USA 82: 6305–6309.

    Google Scholar 

  93. Glomset, J. A. 1980. High-density lipoproteins in human health and disease. Adv. Intern. Med. 25:91–116.

    PubMed  CAS  Google Scholar 

  94. Barbaras, R., X. Collett, H. Chap, and B. Perret. 1994. Specific binding of free apolipoprotein A-I to a high-affinity binding site on HepG2 cells: Characterization of two high–density lipoprotein sites. J. Am. Chem. Soc. 33: 2335–2340.

    Google Scholar 

  95. Leblond, L. Y., L. Marcel. 1991. The amphipathic alpha-helical repeats of apolipoprotein A-I are responsible for binding of high density lipoproteins to HepG2 cells. J. Biol. Chem. 266:6058–6067.

    PubMed  CAS  Google Scholar 

  96. Eisenberg, S. 1984. High density lipoprotein metabolism. J. Lipid Res. 25: 1017–1058.

    PubMed  CAS  Google Scholar 

  97. Johnson, W.J., M.J. Bamberger, R.A. Latta, P.E. Rapp, M.C. Phillips, G.H. Rothblat. 1986. The bidirectional flux of cholesterol between cells and lipoproteins: Effects of phospholipid depletion of high density lipoprotein. J. Biol. Chem. 261: 5766–5776.

    Google Scholar 

  98. Phillips, M.C., W.J. Johnson, G.H. Rothblat. 1987. Mechanisms and consequences of cellular cholesterol exchange and transfer. Biochim. Biophys. Acta 906: 223–276.

    Google Scholar 

  99. Johnson, W. J., G.K. Chacko, M.C. Phillips and G.H. Rothblat. 1990. The efflux of lysosomal cholesterol from cells. J. Biol. Chem. 265:5546–5553.

    PubMed  CAS  Google Scholar 

  100. Bielicki, J.K., W.J. Johnson, R.B. Weinberg, J.M. Glick, G.H. Rothblat. 1992. Efflux of lipid from fibroblasts to apolipoproteins: Dependence on elevated levels of cellular unesterified cholesterol. J. LipidRes. 33: 1699–1709.

    Google Scholar 

  101. Monaco, L., H.M. Bond, K.E. Howell, R. Cortese. 1987. A recombinant apoA-1-protein A hybrid reproduces the binding parameters of HDL to its receptor. EMBOJ. 6: 3253–3260.

    CAS  Google Scholar 

  102. Mendel, C.M., S.T. Kunitake, J.P. Kane, E. Kempner. 1988. Radiation inactivation of binding sites for high density lipoproteins in human fibroblast membranes. J. Biol. Chem. 263: 1314–1319.

    Google Scholar 

  103. Breckenridge, W.C., J. A. Little, P. Alaupovic, C. S. Wang, A. Kuksis, G. Kakis, F. Lindgren, and G. Gardiner. 1982. Lipoprotein abnormalities associated with a familial deficiency of hepatic lipase. Atherosclerosis 45: 161–179.

    Article  PubMed  CAS  Google Scholar 

  104. Koizumi, J., H. Mabuchi, and A. Yoshimura. 1985. Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia. Atherosclerosis 58: 175–186.

    Article  PubMed  CAS  Google Scholar 

  105. Imazu, A., M.L. Brown, C.B. Hesler, L.B. Agellon, J. Koizumi, K. Takata, Y. Maruhama, H. Mabuchi, and A.R. Tall. 1990. Increased high-density lipoprotein levels caused by a common cholesterylester transfer protein gene mutation. New Engl. J. Med. 323: 1234–1238.

    Google Scholar 

  106. Babirak, S.P., P. H. Iverius, W. Y. Fujimoto, and J. D. Brunzell. 1989. The detection of the heterozy gote state for lipoprotein lipase deficiency. Arterioscler. 9: 326–334.

    Article  CAS  Google Scholar 

  107. Weisgraber, K.H., T. P. Bersot, R. W. Mahley, G. Franceschini, and C. R. Sirtori. 1980. A-I Milano apoprotein. Isolation and characterization of a cysteine-containing variant of the A-I apoprotein from human high density lipoproteins. J. Clin. Invest. 66: 901–907.

    Google Scholar 

  108. Franceschini, G., C. R. Sirtori, A. CapursoK. H., Weisgraber, and R. W. Mahley. 1980. Decreased high density lipoprotein cholesterol levels with significant lipoprotein modification and without clinical atherosclerosis in an Italian family. J. Clin. Invest. 66:892–900.

    Article  PubMed  CAS  Google Scholar 

  109. Franceschini, G., M. Baio, L. Calabresi, C. R. Sirtori, and M. C. Cheung. 1990. Apolipoprotein AI Milano. Partial lecithin:cholesterol acyltransferase deficiency due to low levels of a functional enzyme. Biochim. Biophys. Acta 1043: 1–6.

    Google Scholar 

  110. Weisgraber, K.H., S. C. Rail,Jr., T. P. Bersot, R. W. Mahley, G. Franceschini, and C. R. Sirtori. 1983. Apolipoprotein A-IMilano. Detection of normal A-I in affected subjects and evidence for a cysteine for arginine substitution in the variant A-I. J. Biol. Chem. 258: 2508–2513.

    Google Scholar 

  111. Rail, S.C. Jr., K. H. Weisgraber, R. W. Mahley, Y. Ogawa, C. J. Fielding, G. Utermann, J. Haas, A. Steinmetz, H. J. Menzel, and G. Assmann. 1984. Abnormal lecithin:cholesterol acyltransferase activation by a human apolipoprotein A-I variant in which a single lysine residue is deleted. J. Biol Chem. 259: 10063–10070.

    Google Scholar 

  112. Utermann, G., G. Feussner, G. Franceschini, J. Haas, and A. Steinmetz. 1982. Genetic variants of group A apolipoproteins. Rapid methods for screening and characterization without ultracentrifugation. J. Biol. Chem. 257:501–507. 558.

    Google Scholar 

  113. Funke, H., A. von Eckardstein, P. H. Pritchard, M. Karas, J. J. Albers, and G. Assmann: 1991. A frameshift mutation in the human apolipoprotein A-I gene causes high density lipoprotein deficiency, partial lecithin: cholesterol-acyltransferase deficiency, and corneal opacities. J. Clin. Invest. 87: 371–376.

    Google Scholar 

  114. Deeb, S.S., M.C. Cheung, R.L. Peng, A.C. Wolf, R. Stem, J.J. Albers, and R.H. Knopp. 1991. A mutation in the human apolipoprotein A-I gene. Dominant effect on the level and characteristics of plasma high density lipoproteins. J. Biol. Chem. 266: 13654–13660.

    Google Scholar 

  115. Menzel, H.J., G. Assmann, S. C. Rail, Jr., K. H. Weisgraber, and R. W. Mahley. 1984. Human apolipoprotein A-I polymorphism. Identification of amino acid substitutions in three electrophoretic variants of the Munster-3 type. J. Biol. Chem. 259:3070–3076.

    PubMed  CAS  Google Scholar 

  116. Rail, S.C., K. H. Weisgraber, R. W. Mahley, O. Ehnholm, D. Schamaun, B. Olaisen, J. P. Blomhoff, and P. Teisberg. 1986. Identification of homozygosity for a human apolipoprotein A-I variant. J. Lipid Res. 27: 436–441.

    Google Scholar 

  117. Strobl, W., H. U. Jabs, M. Hayde, T. Holzinger, G. Assmann, and K. Widhalm. 1988. Apolipoprotein A-I (Glu 198-Lys): a mutant of the major apolipoprotein of high-density lipoproteins occurring in a family with dyslipoproteinemia. Pediatr. Res. 24: 222–228.

    Google Scholar 

  118. Nichols, W.C., F. E. Dwulet, J. Liepnieks, and M. D. Benson. 1988. Variant apolipoprotein AI as a major constituent of a human hereditary amyloid. Biochem. Biophys. Res. Commun. 156: 762–768.

    Google Scholar 

  119. Nichols, W.C., R. E. Gregg, H. B. Brewer,Jr., and M. D. Benson. 1990. A mutation in apolipoprotein A-I in the Iowa type of familial amyloidotic polyneuropathy. Genomics 8: 318–323.

    Article  PubMed  CAS  Google Scholar 

  120. Jeenah, M., A. Kessling, N. Miller, and S. Humphries. 1990. G to A substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI and high density lipoprotein cholesterol concentrations. Molec. Biol. Med. 7: 233–241.

    Google Scholar 

  121. Matsunaga, T., Y. Hiasa, H. Yanagi, T. Maeda, N. Hattori, K. Yamakawa, Y. Yamanouchi, I. Tanaka, T. Obara, and H. Hamaguchi. 1991. Apolipoprotein A-I deficiency due to a codon 84 nonsense mutation of the apolipoprotein A-I gene. Proc. Natl. Acad. Sci USA 88: 2793–2797.

    Google Scholar 

  122. Breslow, J.L. 1989. Familial disorders of high density lipoprotein metabolism. In “The Metabolic Basis of Inherited Disease”. C. R. Scriver, A. I. Beaudet, W. S. Sly, and D. Valle, editors. McGraw-Hill, New York. 1251–1266.

    Google Scholar 

  123. Schonfeld, G. 1990. The genetic dyslipoproteinemias-nosology update 1990. Atherosclerosis 81: 81–93.

    Article  PubMed  CAS  Google Scholar 

  124. von Eckardstein, A., H. Funke, A. Henke, K. Altland, A. Benninghoven, and G. Assmann. 1989. Apolipoprotein A-I variants..Naturally occurring substitutions of proline residues affect plasma concentration of apolipoprotein A-I. J. Clin. Invest. 84: 1722–1730.

    Google Scholar 

  125. Jonas, A., A. von Eckardstein, K. E. Kézdy, A. Steinmetz, and G. Assmann. 1991. Structural and functional properties of reconstituted high density lipoprotein discs prepared with six apolipoprotein A-I variants. J. Lipid Res. 32: 97–106.

    PubMed  CAS  Google Scholar 

  126. Schaefer, E.J., J.M. Ordovas, S.W. Law, G. Ghiselli, ML. Kashyap, L.S. Srivastava, W.H. Heaton, J.J. Albers, W.E. Connor, F.T. Lindgren, Y. Lemeshev, J.P Segrest, and H.B. Brewer Jr. 1985. Familial apolipoprotein A-I and C-III deficiency, variant II. J. Lipid Res. 26: 1089–1101.

    PubMed  CAS  Google Scholar 

  127. Ordovas, J.M., D.K. Cassidy, F. Civeira, C.L. Bisgaier, and E.J. Schaefer. 1989. Familial apolipoprotein A-I, C-III, and A-IV deficiency and premature atherosclerosis due to deletion of a gene complex on chromosome 11. J. Biol. Chem. 264: 16339–16342.

    Google Scholar 

  128. Norum R. A. 1982. Familial deficiency of apolipoproteins AI and CIII and precocious coronary artery disease. New Engl. J. Med 306:1513–1519.

    Google Scholar 

  129. Karathanasis, S.K., E. Ferris, and I. A. Haddad. 1987. DNA inversion within the apolipoproteins AI/CIII/AI V-encoding gene cluster of certain patients with premature atherosclerosis. Proc. Natl. Acad. Sci USA 84: 7198–7202.

    Google Scholar 

  130. Karathanasis S.K., V.I. Zannis, J.L. Breslow. 1983. A DNA insertion has occurred in the apoli poprotein A-I gene of patients with premature atherosclerosis. Nature 305: 823–825.

    Article  PubMed  CAS  Google Scholar 

  131. Karathanasis, S.K., McPherson, J., Zannis, V.I., Breslow, J.L. 1983. Linkage of human apolipoprotein A–I and C–III genes. Nature 304: 371–373.

    Article  PubMed  CAS  Google Scholar 

  132. Papazafiri, P., Ogami, K., Ramji, D.P., Nicosia, A., Monaci, P., Cladaras, C., and Zannis, V.I. 1991. Promoter elements and factors involved in hepatic transcription of the human apoA-I gene positive and negative regulators bind to overlapping sites. J. Biol. Chem. 266: 5790.

    Google Scholar 

  133. Zannis, V.I., D. Kardassis, P. Cardot, M. Hadzopoulou-Cladaras, E.E. Zanni and C. Cladaras. 1992. Molecular biology of the human apolipoprotein genes: Gene regulation and structure-function relationship. Curr. Opin. Lipid. 3: 96–113.

    Google Scholar 

  134. Zannis, V.I., C. Cladaras, and I. Talianidis. 1994. The role of the hormone response elements (HRE) and the apoCIII enhancer on the transcriptional regulation of genes involved in lipid transport. Xth International Symposium on Atherosclerosis. Montreal 1994. (in press).

    Google Scholar 

  135. Tzameli, E., C. Cladaras, and V.I. Zannis. 1993. Effect of mutations in the nuclear receptor response element of apoA-I on transcription and the binding of homo-and heterodimeric complexes of nuclear receptors. Circulation 88: 422.

    Google Scholar 

  136. Walsh, A., N. Azrolan, K. Wang, A. Marcigliano, A. O’Connel, and J.L. Breslow. 1993. Intestinal expression of the human apoA-I gene is controlled by a DNA region, 3’ to the gene in the promoter of the adjacent convergently transcribed apoCIII gene. J. Lipid Res. 34: 617.

    PubMed  CAS  Google Scholar 

  137. Rail, S.C., K. H. Weisgraber and R. W. Mahley. 1981. Human apolipoprotein E: The complete amino acid sequence. J. Biol Chem. 257: 4171–4178.

    Google Scholar 

  138. Zannis, V.I., J. McPherson, G. Goldberger, S.K. Karathanasis and J.L. Breslow. 1984. Synthesis, intracellular processing and signal peptide of human apoE. J. Biol. Chem. 259: 5495–5499.

    Google Scholar 

  139. Paik, Y.K., D. J. Chang, C. A. Reardon, G. E. Davies, R. W. Mahley and J. M. Taylor. 1985. Nucleotide sequence and structure of the human apolipoprotein E gene. Proc. Natl. Acad. Sci USA 82: 3445–3451.

    Google Scholar 

  140. Das, H.K., J. McPherson, G.A.P. Bruns, S.K. Karathanasis, and J.L. Breslow. 1985. Isolation, characterization and mapping to chromosome 19 of the human apolipoprotein E gene. J. Biol. Chem. 260: 6240–6246.

    Google Scholar 

  141. McLean, J.W., N.A. Elshourbagy, D.J. Chang, R.W. Mahley, and J.M. Taylor. 1984. Human apolipoprotein E mRNA. cDNA cloning and nucleotide sequencing of a new variant. J. Biol. Chem. 259: 6498–7504.

    Google Scholar 

  142. Wetterau, J.R., L.P. Aggerbeck, S.C. Rail, Jr. and K.H. Weisgraber. 1988. Human apolipoprotein E3 in aqueous solution. I. Evidence for two structural domains. J. Biol. Chem. 263:6240–6248.

    PubMed  CAS  Google Scholar 

  143. Aggerbeck, L.P, J.R. Wetterau, K.H. Weisgraber, C.S.C. Wu and F.T. Lindgren. 1988. Human apolipoprotein E3 in aqueous solution. II. Properties of the amino-and carboxyl-terminal domains. J. Biol. Chem. 263: 6249–6258.

    Google Scholar 

  144. Innerarity, T.L., E.J. Friedlander, S.C. Rail, Jr., K.H. Weisgraber and R.W. Mahley. 1983. The receptor-binding domain of human apolipoprotein E. Binding of apolipoprotein E fragments. J. Biol. Chem. 258: 12341–12347.

    Google Scholar 

  145. Weisgraber, K.H., T.L. Innerarity, K.J. Harder, R.W Mahley, R.W. Milne, Y.L. Marcel and J.T. Sparrow. 1983. The receptor-binding domain of human apolipoprotein E. J. Biol. Chem. 258: 12348–12354.

    Google Scholar 

  146. Zannis, V.I., C. Cladaras and E.E. Zanni. 1991. Apolipoprotein and lipoprotein synthesis and modifica tions. Current Opin. Lipid. 2: 149–155.

    Google Scholar 

  147. Newman, T.C., PA. Dawson, L.L. Rudel., and D.L. Williams. 1985. Quantitation of apolipoprotein EmRNA in the liver and peripheral tissues of nonhuman primates. J. Biol. Chem. 260: 2452–2457.

    Google Scholar 

  148. Pitas, R.E., T.L. Innerarity and R. W. Mahley. 1980. Cell surface receptor binding of phospholipid-protein complexes containing different ratios of receptor-active and inactive E apoprotein. J. Biol. Chem. 255: 5454–5460.

    Google Scholar 

  149. Lalazar, A., K.H. Weisgraber, S.C. Rail Jr., H. Giladi, T.L. Innerarity, A.Z. Levanon, J.K. Boyles, B. Amit, M. Gorecki and R.W. Mahley. 1988. Site-specific mutagenesis of human apolipoprotein E. Receptor binding activity of variants with single amino acid substitutions. J. Biol. Chem. 263: 3542–3545.

    Google Scholar 

  150. Lalazar, A. and R. W. Mahley. 1989. Human apolipoprotein E. Receptor binding activity of truncated variants with carboxyl-terminal deletions. J. Biol Chem. 264: 8447–8450.

    Google Scholar 

  151. Cladaras, C., M. Hadzopoulou-Cladaras, R.T. Nolte, D. Atkinson and V.I. Zannis (1986) The complete sequence and structural analysis of human apolipoprotein B-100: Relationship between apoB-100 and apoB-48 forms. EMBOJ. 5: 3495–3508.

    CAS  Google Scholar 

  152. Weisgraber, K.H., S.C. Rail, Jr., R.W. Mahley, R.W. Milne, Y.L. Marcel, and J.T. Sparrow. 1986. Human apolipoprotein E. J. Biol Chem. 261: 2068–2076.

    CAS  Google Scholar 

  153. Cardin, A.D., N. Hirose, D.T. Blankenship, R.L. Jackson, and J.A.K. Harmony. 1986. Binding of a high reactive heparin to human apolipoprotein E: Identification of two heparin-binding domains. Biochem. Biophys. Res. Commun. 134: 783–789.

    Google Scholar 

  154. Weisgraber K.H. 1990. Apolipoprotein E distribution among human plasma lipoproteins: role of the cysteine-arginine interchange at residue 112. J. Lipid Res. 31: 1503–1511

    CAS  Google Scholar 

  155. Gregg R.E., L.A. Zech, E.J. Schaefer, D. Stark, D. Wilson, H.B. Brewer Jr. 1986. Abnormal in vivo metabolism of apolipoprotein E4 in humans. J. Clin. Invest. 78: 815–821.

    Google Scholar 

  156. Hefele Wald J., Goormaghtigh E., De Meutter J., Ruysschaert J.M. and Jonas A. 1990. Investigation of the lipid domains and apolipoprotein orientation in reconstituted high density lipoproteins by fluorescence and I.R. methods. J. Biol Chem. 265: 20044–20050

    Google Scholar 

  157. Lund-Katz S., Weisgraber K.H., Mahley R.W. and Phillips M.C. 1993. Conformation of apolipoprotein E. J; Biol. Chem. 268: 23008–23015.

    Google Scholar 

  158. Pitas, R.E., J.K. Boyles, S.H. Lee, D. Foss and R.W. Mahley. 1987. Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins. Biochim. Biophys. Acta 917: 148–161.

    Google Scholar 

  159. Mahley, R.W. 1988. Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology. Science 240:622–630.

    Article  PubMed  CAS  Google Scholar 

  160. Muller, H. W., M. J.. Ignatius, D.H. Hanagen and E.M. Shooter. 1986. Expression of specific sheath cell proteins during peripheral nerve growth and regeneration in mammals. J. Cell Biol 102: 393–402.

    Article  PubMed  CAS  Google Scholar 

  161. Ignatius, M.J., P.J. Gebicke-Harter, J.H.P. Skene, J.W. Schilling, K.H. Weisgraber, R.W. Mahley and E.M. Shooter. 1986. Expression of apolipoprotein E during nerve degeneration and regeneration. Pwc. Natl Acad. Sci USA 83: 1125–1129.

    Google Scholar 

  162. Pitas, R.E., J.K. Boyles, S.H. Lee, D. Hui and K.H. Weisgraber. 1987. Lipoproteins and their receptors in the central nervous system. J. Biol Chem. 262: 14352–14360.

    PubMed  CAS  Google Scholar 

  163. Boyles, J., C.D. Zoellner, L.J. Anderson, L.M. Kosik, R.E. Pitas, K.H. Weisgraber, D.Y. Hui, R.W. Mahley, P.J. Gebicke-Harter, M.J. Ignatius and E.M. Shooter. 1989. A role of apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve. J. Clin. Invest. 83: 1015–1031.

    Google Scholar 

  164. Gwynne, J.T. and B. Hess. 1980. The role of high density lipoproteins in rat adrenal cholesterol metabolism and steroidogenesis. J. Biol Chem. 255: 10875–10883.

    PubMed  CAS  Google Scholar 

  165. Gordon, V., T.L. Innerarity and R.W. Mahley. 1983. Formation of cholesterol-and apoprotein E-enriched high density lipoproteins in vitro. J. Biol Chem. 258: 6202–6212.

    PubMed  CAS  Google Scholar 

  166. Kowal, R.C., J. Herz, K.H. Weisgraber, R.W. Mahley, M.S. Brown, J.L. Goldstein. 1990. Opposing effects of apo-E and C on lipoprotein binding to low density lipoprotein receptor–related protein. J. Biol Chem. 265: 10771–10779.

    PubMed  CAS  Google Scholar 

  167. Weisgraber, K.H., R.W. Mahley, R.C. Kowal, J. Here, J.L. Goldstein and M.S. Brown. 1990. Apolipoprotein C-I modulates the interaction of apolipoprotein E with beta-migrating very low density lipoprotein (beta-VLDL) and inhibits binding of beta-VLDL to low density lipoprotein receptor-related protein. J. Biol Chem. 265: 22453–22459.

    CAS  Google Scholar 

  168. Reyland, M.E., J.T. Gwynne, P. Forgez, M.M. Prack and D.L. Williams. 1991. Expression of the human apolipoprotein E gene suppresses steroidogenesis in mouse Y1 adrenal cells. Pwc. Natl Acad. Sci USA 88: 2375–2379.

    Google Scholar 

  169. Ehnholm, C., R.W. Mahley, D.A. Chappell, K.H. Weisgraber, E. Ludwig, and J.L. Witztum. 1984. Role of apolipoprotein E in the lipolytic conversion of beta-very low density lipoproteins to low density lipoproteins in type III hyperlipoproteinemia. Pwc. Natl Acad. Sci. USA 81: 5566–5570.

    Google Scholar 

  170. Zannis, V.I., P. W. Just and J. L. Breslow. 1981. Human apolipoprotein E isoprotein subclasses are genetically determined. Am. J. Hum. Genet. 33: 11–24.

    Google Scholar 

  171. Zannis, V.I., J. L. Breslow, G. Utermann, R. W. Mahley, K. H. Weisgraber, R. J. Havel, J. L. Goldstein, M. S. Brown, G. Schonfeld, W. R. Hazzard and C. B. Blum. 1982. Proposed nomenclature of apoE isoprotein genotypes and phenotypes. J. Lipid Res. 23: 911–914.

    PubMed  CAS  Google Scholar 

  172. Zannis, V.I. and J. L. Breslow. 1981. Human very low density lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and post-translational modification. Biochemistry 20: 1033–1041.

    CAS  Google Scholar 

  173. Davignon, J., R.E. Gregg and C.F. Sing. 1988. Apolipoprotein E polymorphism and atherosclerosis. Arterioscler. 8: 1–21.

    CAS  Google Scholar 

  174. Breslow, J.L. and V. I. Zannis. 1986. Genetic variation in apolipoprotein E and type III hyperlipoproteinemia. Arterioscler. Rev. 14: 119–141.

    Google Scholar 

  175. Zannis, V.I. 1989. Molecular biology of human apolipoproteins B and E and associated diseases of lipoprotein metabolism. In: “Advances in Lipid Research”. Vol. 23, pp. 1–64, Academic Press, San Diego, CA.

    Google Scholar 

  176. Utermann, G. 1985. In “Diabetes, Obesity and Hyperlipidemias”. G. Crepaldi, A. Tiengo and G. Baggio, editors. Excerpta Medica, Amsterdam. 1–28.

    Google Scholar 

  177. Utermann, G. 1985. ApoE mutants, hyperlipidemia and arteriosclerosis. Adv. Exp. Med. Biol 183: 173–188.

    Google Scholar 

  178. Sing, C.F. and J. Davignon. 1985. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am. J. Hum. Genet. 37: 268–285.

    Google Scholar 

  179. Assmann, G., G. Schmitz, H. J. Menzel, and H. Schultz. 1984. Apolipoprotein E polymorphism and hyperlipidemia. Clin. Chem. 30: 641–643.

    Google Scholar 

  180. Lussier-Cacan, S., D. Bouthillier, and J. Davignon. 1985. ApoE allele frequency in primary endogenous hypertriglyceridemia (type IV) with and without hyperapobetalipoproteinemia. Arterioscler. 5: 639–643.

    Article  CAS  Google Scholar 

  181. Eto, M., K. Watanabe, Y. Iwashima, A. Morikawa, E. Oshima, M. Sekiguchi, and K. Ishii. 1986. Apolipoprotein E polymorphism and hyperlipemia in type II diabetics. Diabetes 35: 1374–1382.

    CAS  Google Scholar 

  182. Leren, T.P, A. L. Borresen, K. Berg, P. Hjermann, and P. Leren. 1985. Increased frequency of the apolipoprotein E-4 isoform in male subjects with multifactorial hypercholesterolemia. Clin. Genet. 27: 458–462.

    Google Scholar 

  183. Utermann, G., A. Hardewig, and F. Zimmer. 1984. Apolipoprotein E phenotypes in patients with myocardial infarction. Human. Genetics 65: 237–241.

    Google Scholar 

  184. Goldstein, J.L. and M.S. Brown. 1983. Familial hypercholesterolemia. In: “The Metabolic Basis of Inherited Disease”. ( J.B. Stanbury, J. Wyngaarden and D.S. Fredrickson, eds.) McGraw-Hill, New York. pp. 672–712.

    Google Scholar 

  185. Mahley, R.W. and S.C. Rail, Jr. 1989. Type III hyperlipoproteinemia (Dysbetalipoproteinemia): The role of apolipoprotein E in normal and abnormal lipoprotein metabolism. In: “The Metabolic Basis of Inherited Disease”. ( C.R. Scriver, A.I. Beaudet, W.S. Sly and D. Valle, eds.) McGraw-Hill, New York. pp. 1195–1211.

    Google Scholar 

  186. Breslow, J.L., V.I. Zannis, R.R. SanGiacomo, J.L.H.C. Third, T. Tracy and C.J. Glueck. 1982. Studies of familial type III hyperlipoproteinemia using as a genetic marker the apoE phenotype E2/2. J. Lipid Res. 23: 1224–1235.

    PubMed  CAS  Google Scholar 

  187. Havel, R.J., L. Kotite, J.L. Vigne, J.P Kane, P. Tun, N. Phillips and G.C. Chen. 1980. Radioimmunoassay of human arginine-rich apolipoprotein, apoprotein E. Concentration in blood plasma and lipoproteins as affected by apoprotein E-3 deficiency. J. Clin. Invest. 66: 1351–1362.

    Google Scholar 

  188. Havel, R. J. and J.L. Kane. 1973. Primary dysbetalipoproteinemia: Predominance of a specific apoprotein species in triglyceride-rich lipoproteins. Pwc. Natl. Acad. Sci USA 70: 2015–2019.

    Google Scholar 

  189. Mahley, R.W., T.L. Innerarity, S.C. Rail, Jr., K.H. Weisgraber and J.M. Taylor. 1990. Apolipoprotein E: genetic variants provide insights into its structure and function. Curr. Opin. Lipid 1: 87–95.

    Google Scholar 

  190. Bersot, T.P., T.L. Innerarity, R. W. Mahley and R. J. Havel. 1983. Cholesteryl ester accumulation in mouse peritoneal macrophages induced by beta-migrating very low density lipoproteins from patients with atypical dysbetalipoproteinemia. J. Clin. Invest. 72 (3): 1024–1033.

    Article  PubMed  CAS  Google Scholar 

  191. Havel, R. J., L. Kotite, J.P. Kane, P. Tun and T. Bersot. 1983. Atypical familial dysbetalipoproteinemia associated with apolipoprotein phenotype E3/3. J. Clin. Invest. 72: 379–387.

    Google Scholar 

  192. Wardell, M.R., S.O. Brennan, E.D. Janus, R. Fraser, and R.W. Carrell. 1987. Apolipoprotein E2-Christchurch (136Arg-Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia. J. Clin. Invest. 80: 483–490.

    Google Scholar 

  193. Rail, S.C. Jr., Y.M. Newhouse, H.R.G. Clarke, K.H. Weisgraber, B.J. McCarthy, R.W. Mahley and T.P. Bersot. 1989. Type III hyperlipoproteinemia associated with apolipoprotein E phenotype E3/3: structure and genetics of an apolipoprotein E3 variant. J. Clin. Invest. 83: 1095–1101.

    Google Scholar 

  194. Mann, W.A., R.E. Gregg, D.L. Sprecher, and H.B. Brewer, Jr. 1989. Apolipoprotein E-lHarrisburg: a new variant of apolipoprotein E dominantly associated with type III hyperlipoproteinemia. Biochim. Biophys. Acta 1005: 239–244.

    Google Scholar 

  195. Wardell, M.R., K.H. Weisgraber, L.M. Havekes, and S.C. Rail, Jr. 1989. Apolipoprotein E3-Leiden contains a seven-amino acid insertion that is a tandem repeat of residues 121–127. J. Biol. Chem. 264: 21205–21210.

    Google Scholar 

  196. van den Maagdenberg, A.M., P. de Knijff, A.F. Stalenhoef, J.A. Gevers Leuven, L.M. Havekes and R.R. Frants. 1989. Apolipoprotein E 3-Leiden allele results from a partial gene duplication in exon 4. Biochem. Biophys. Res. Commun. 165: 851–857.

    Google Scholar 

  197. Smit, M., P. de Knijff, E. van der Kooij-Meijs, C. Groenendijk, A.M. van den Maagdenberg, J.A. Gevers Leuven, A.F. Stalenhoef, P.M. Stuyt, R.R. Frants and L.M. Havekes. 1990. Genetic heterogeneity in familial dysbetalipoproteinemia. The E2(lysl46-gin) variant results in a dominant mode of inheritance. J. Lipid Res. 31: 45–53.

    PubMed  CAS  Google Scholar 

  198. Weisgraber, K.H., S.C. Rail Jr., T.L. Innerarity and R.W. Mahley. 1984. A novel electrophoretic variant of human apolipoprotein E: Identification and characterization of apolipoprotein El.J. Clin. Invest. 73: 1024–1033.

    Google Scholar 

  199. Steinmetz, A., N. Assefbarkhi, C. Eltze, K. Ehlenz, H. Funke, A. Pies, G. Assmann, and H. Kaffarnik. 1990. Normolipemic dysbetalipoproteinemia and hyperlipoproteinemia type III in subjects homozygous for a rare genetic apolipoprotein E variant (apoE 1). J. Lipid Res. 31: 1005 - 1013.

    CAS  Google Scholar 

  200. Wardell, M.R., S.C. Rail Jr., E.J. Schaefer, J.P. Kane and K.H. Weisgraber. 1991. Two apolipoprotein E5 variants illustrate the importance of the position of additional positive charge on recep-tor-binding activity. J. Lipid Res. 32: 521–528.

    PubMed  CAS  Google Scholar 

  201. Maeda, H., H. Nakamura, S. Kobori, M. Okada, H. Mori, H. Niki, T. Ogura, and S. Hiraga. 1989. Identification of human apolipoprotein E variant gene: apolipoprotein E7 (Glu244,245-Lys 244,245). J. Biochem. 105: 51–54.

    CAS  Google Scholar 

  202. Tajima S., T. Yamamura, M. Menju, A. Yamamoto. 1989. Analysis of apolipoprotein E7 (apolipoprotein E-Suita) gene from a patient with hyperlipoproteinemia. J. Biochem. 105: 249–253.

    PubMed  CAS  Google Scholar 

  203. Lohse P., W.A. Mann, E.A. Stein, H.B. Brewer Jr. 1991. Apolipoprotein E-4 Philadelphia (Glu 13-Lys, Argl45-Cys). Homozygosity for two rare point mutations in the apolipoprotein E gene combined with severe type III hyperlipoproteinemia. J. Biol. Chem. 266: 10479–10484.

    Google Scholar 

  204. Mailly, F., C. F. Xu, M. Xhignesse, S. Lussier-Cacan, P. J. Talmud, J. Davignon, S. E. Humphries, A. C. Nestruck. 1991. Characterization of a new apolipoprotein E5 variant detected in two French-Canadian subjects. J. Lipid Res. 32: 613–620.

    PubMed  CAS  Google Scholar 

  205. van den Maagdenberg, A.M., W. Weng, I.H. de Bruijn, P. de Knijff, H. Funke, A.H. Smelt, J.A. Gebers Leuven, F.M. van’t Hooft, G. Assmann, M.H. Hofker. 1993. Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: No cosegregation with severe hyperlipidemia. Am. J. Hum. Genet. 52: 937–946.

    Google Scholar 

  206. Ruzicka, V., W. Marz, A. Russ, E. Fisher, W. Mondorf, W. Gross. 1993. Characterization of the gene for apolipoprotein E5-Frankfurt (Gln71-Lys, Cysl 12-Arg) by polymerase chain reaction, restriction isotyping, and temperature gradient gel electrophoresis. Electrophoresis 14: 1032–1037.

    Article  PubMed  CAS  Google Scholar 

  207. Innerarity T.L., D. Y. Hui, T.P. Bersot, R.W. Mahley. 1986. Type III hyperlipoproteinemia: A focus on lipoprotein receptor-apolipoprotein E2 interactions. Adv. Exp. Med. Biol. 201: 273–288.

    Google Scholar 

  208. Fredrickson, D.S. and R.I. Levy. 1972. Familial hyperlipoproteinemia in: “The Metabolic Basis of Inherited Disease”. (J.B. Stanbuiy, J.B. Wyngaarden, and D.S. Fredrickson, eds.), McGraw-Hill, New York, pp. 545–614.

    Google Scholar 

  209. Utermann, G., K. H. Vogelberg, A. Steinmetz, W. Schoenborn, N. Pruin, M. Jaeschke, M. Hees and H. Canzler. 1979. Polymorphism of apolipoprotein E. II. Genetics of hyperlipoproteinemia type III. Clin. Genet. 15: 37–62.

    Google Scholar 

  210. Hazzard W.R., G.R. Warnick, G. Utermann, J.J. Albers. 1981. Genetic transmission of isoapolipoprotein E phenotypes in a large kindred: Relationship to dysbetalipoproteinemias and hyperlipidemia. Metabolism: Clinical and Experimental 30: 79–89.

    Google Scholar 

  211. Marien J.K., H. A. Hulsmans, C.M. vanGent. 1974. On a family with coexistence of phenotypes II and III hyperlipoproteinemia. Acta Med. Scand. 196: 149–153.

    Google Scholar 

  212. Morganroth, J., Levy, R.I., and Fredrickson, D.S. 1975. The Biochemical, Clinical, and Genetic Features of Type III Hyperlipoproteinemia. Ann. Intern. Med. 82: 158–174.

    Google Scholar 

  213. Hazzard, W.R., and Bierman, E.L 1972. Aggravation of broad-B disease (type III hyperlipoproteinemia) by hypothyroidism. Arch. Intern. Med. 130: 822–828.

    Google Scholar 

  214. Ghiselli, G., E.J. Schaefer, P. Gascon, and H.B. Breser Jr. 1981. Type III hyperlipoproteinemia associated with apolipoprotein E deficiency. Science 214: 1239–1241.

    CAS  Google Scholar 

  215. Schaefer, E.J., R.E. Gregg, G. Ghiselli, T.M. Forte, J.M. Ordovas, L.A. Zech, and H.B. Brewer. 1986. Familial apolipoprotein E deficiency. J. Clin. Invest. 78: 1206–1219.

    Google Scholar 

  216. Zannis, V.I., J.M. Ordovas, C. Cladaras, F.S. Cole, G. Forbes and E.J. Schaefer. 1985. mRNA and apolipoprotein E synthesis abnormalities in peripheral blood monocyte macrophages in familial apolipoprotein E deficiency. J. Biol. Chem. 24: 12891–12894.

    Google Scholar 

  217. Cladaras, C., M. Hadzopoulou-Cladaras, B.K. Felber, G. Pavlakis, and V.I. Zannis. 1987. The molecular basis of a familial apoE deficinecy. An acceptor splice site mutation in the third intron of the deficient apoE gene. J. Biol. Chem. 262: 2310–2315.

    Google Scholar 

  218. Smith, J.D., Plump, A.S., Hayek, T., Breslow, J.L. 1990. Accumulation of human apolipoprotein E in the plasma of transgenic mice. J. Biol. Chem\ 265: 14709–14712.

    Google Scholar 

  219. Shimano H., N. Yamada, M. Katsuki, M. Shimada, T. Gotoda, K. Harada, T. Murase, C. Fukazawa, F. Takaku, Y. Yazaki. 1992. Overexpression of apolipoprotein E in transgenic mice: Marked reduction in plasma lipoprotein except high density lipoprotein and resistance against diet–induced hypercholesterolemia. Proc. Natl. Acad. Sci. USA 89: 1750–1754.

    Google Scholar 

  220. Shimano H., N. Yamada, M. Katsuki, K. Yamamoto, T. Gotoda, K. Harada, M. Shimada, Y. Yazaki. 1992. Plasma lipoprotein metabolism in transgenic mice overexpressing apolipoprotein E. J. Clin. Invest. 90: 2084–2091.

    Google Scholar 

  221. Piedrahita J.A., S.H. Zhang, J.R. Hagaman, P.M. Oliver, N. Maeda. 1992. Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc. Natl. Acad. Sci. USA 89: 4471–4475.

    Google Scholar 

  222. Van den Maagdenberg A.M.J., M.H. Hofker, P.J.A. Krimpenfort, I. De Bruijn, B. Van Vlijmen, H. van der Boom, L.M. Havekes, R.R. Frants. 1993. Transgenic mice carrying the apolipoprotein E3-Leiden gene exhibit hyperlipoproteinemia. J. Biol. Chem. 268: 10540–10545.

    Google Scholar 

  223. Fazio S., Y. Lee, X. Sheng, S.C. Rail Jr. 1993. Type III hyperlipoproteinemic phenotype in transgenic mice expressing dysfunctional apolipoprotein. J. Clin. Invest. 92: 1497–1503.

    Google Scholar 

  224. Fazio S., Y. Horie, W.S. Simonet, K.H. Weisgraber, J.M. Taylor, S.C. Rail Jr. 1994. Altered lipoprotein metabolism in transgenic mice expressing low levels of a human receptor-binding-defective apolipoprotein E variant. J. Lipid Res. 35: 408–416.

    CAS  Google Scholar 

  225. Fazio S., D.A. Sanan, Y–L. Lee, Z-S. Ji, R.W. Mahley, S.C. Rail Jr. 1994. Susceptibility to diet-induced atherosclerosis in transgenic mice expressing a dysfunctional human apolipoprotein E (Argl 12, Cysl42). Arterioscler. Thwmb. 14: 1873–1879.

    Google Scholar 

  226. Wisniewski, T., Golabek, A., Matsubara, E., Ghiso, J. and Frangione, B. (1993) Apolipoprotein E: binding to soluble Alzheimer’s P–amyloid. Biochem. Biophys. Res. Commun. 192: 359–365.

    Google Scholar 

  227. Sanan, D.A., K.H. Weisgraber, S.J. Russell, R.W. Mahley, D. Hunng, A. Saunders, D. Schmochol, T. Wianlowski, B. Frangiono, A.D. Roses and W.J. Strittmatter. 1994. Apolipoprotein E associates with p amyloid peptide of Alzheimer’s disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3. J. Clin. Invest. 94: 860–869.

    Google Scholar 

  228. Strittmatter, W.J., K.H. Weisgraber, M. Goedert, A.M.Saunders, D. Huang, E.H. Corder, L.-M. Dong, R. Jakes, M.J. Alberts, J.R. Gilbert, S.-H. Han, C. Hulette, G. Einstein, D.E. Schmechel, M.A. Pericak-Vance and A.D. Roses. 1994. Hypothesis: Microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype. Exper. Neuml. 125: 163–171.

    Google Scholar 

  229. Nathan, B.P., S. Bellosta, D.A. Sanan, K.H. Weisgraber, R.W. Mahley and R.E. Pitas. 1994. Differential effects of apolipoprotein E3 and E4 on neuronal growth in vitro. Science 264: 850.

    Article  PubMed  CAS  Google Scholar 

  230. Ponte, P., P. Gonzalez-DeWhitt, J. Schilling, J. Miller, D. Hus, B. Greenberg, K. Davis, W. Wallace, I. Lieberburg, F. Fuller and B. Cordell. 1988. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature 331: 525–527.

    Article  PubMed  CAS  Google Scholar 

  231. Tanzi, R.E., A.I. McClatchey, E.D. Lamperti, L.L. Villa-Komaroff, J.F. Gueslla, R.L. Neve. 1988. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer’s disease. Nature 331: 528–530.

    Article  PubMed  CAS  Google Scholar 

  232. Kitaguchi N., Y. Takahashi, Y. Tolkushima, S. Shiojiri, H. Ito. 1988. Novel precursor of Alzheimer’s disease amyloid protein shows protease inhibitory activity. Nature 331: 530–532.

    Article  PubMed  CAS  Google Scholar 

  233. Selkoe D.J., M.B. Podisny, C.L. Joachim, E.A. Vickers, G. Lee, T. Oltersdorf. 1988. P–Amyloid precursor protein of Alzheimer disease occurs as 110-to 135-kilodalton membrane-associated proteins in neural and non–neural tissues. Proc. Natl. Acad. Sci. USA 85: 7341–7345.

    Google Scholar 

  234. Esch F.S., PS. Keim, E.C. Beattie, R.W. Blacher, A.R. Culwell, T. Oltersdorf, D. McClure, P.J. Ward. 1990. Cleavage of amyloid P peptide during constitutive processing of its precursor. Science 248: 1122–1124.

    Article  PubMed  CAS  Google Scholar 

  235. Sisodia S.S., E.H. Koo, K. Beyreuther, A. Unterbeck, D.L. Price. 1990. Evidence that beta–amyloid protein in Alzheimer’s disease is not derived by normal processing. Science 248: 492–495.

    Article  PubMed  CAS  Google Scholar 

  236. Goate A., M.-C. Chartier-Harlin, M. Mullan. 1991. Segregation of a missense mutation in the amyloid precursor protein with familial Alzheimer’s disease. Nature 349: 704–706.

    Article  PubMed  CAS  Google Scholar 

  237. Chartier-Harlin M.-C., F. Crawford, H. Houlden. 1991. Early-onset Alzheimer’s disease caused by mutations at codon 717 of the p amyloid precursor protein gene. Nature 353: 844–846.

    Article  PubMed  CAS  Google Scholar 

  238. Murrell J., M. Farlow, B. Ghetti, M.D. Benson. 1991. A mutation in the amyloid precursor protein associated with hereditary Alzheimer’s disease. Science 254: 97–99.

    Article  PubMed  CAS  Google Scholar 

  239. Mullan M., F. Crawford, K. Axelman, H. Houlden, L. Lilius, B. Winblad, L. Lannfeldt. 1993. A pathogenic mutation for probable Alzheimer’s disease in the APP gene at the N-terminus of bamyloid. Nature Genet. 1: 345–347.

    Article  Google Scholar 

  240. Levy E., M.D. Carman, I.J. Fernandez–Madrid, M.D. Power, I. Lieberburg, S.G. van Duinen, G.T.A.M. Bots, W. Luyendijk and B. Frangione. 1990. Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage, Dutch–type. Science 248: 1124–1126.

    Google Scholar 

  241. Schellenberg, G.D., T.D. Bird, E.M. Wijsman, H.T. Orr, L. Anderson. E. Nemens, White, Genetic linkage evidence for a familial Alzheimer’s disease locus on chromosome 14. Science 258: 668–671.

    Google Scholar 

  242. Pericak-Vance M.A., J.L. Bebout, PC. Gaskell. 1991. Linkage studies in familial Alzheimer’s disease: Evidence for chromosome 19 linkage. Am. J. Hum. Genet. 48: 1034–1050.

    Google Scholar 

  243. Moorjani, S., M. Roy, A. Torres, C. Betard, C. Gagne, M. Lambert, D. Brun, J. Davignon, P. Lupien. 1993. Mutations of low-density-lipoprotein-receptor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hypercholesterolemia. Lancet 341: 1303–1306.

    Article  PubMed  CAS  Google Scholar 

  244. Leitersdorf, E., A. Reshef, V. Meiner, E.J. Dann, Y. Beigel, F.G. Roggen, D.R. van der Westhuyzen, G.A. Coetzee. 1993. A missense mutation in the low density lipoprotein receptor gene causes familial hypercholesterolemia in Sephardic Jews. Hum. Genet. 91: 141–147.

    Google Scholar 

  245. Yamakawa-Kobayashi, K., T. Kobayashi, K. Saku, K. Arakawa, H. Hamaguchi. 1993. Two novel frameshift mutations associated with the presence of direct repeats of hte LDL receptor gene in familial hypercholesterolemia. Hum. Genet. 92: 331–335.

    Google Scholar 

  246. Miyake, Y., S. Tajima, T. Funahashi, T. Yamamura, A. Yamamoto. 1992. A point mutation of low-density-lipoprotein receptor causing rapid degradation of the receptor. Eur. J. Biochem. 210: 1–7.

    Google Scholar 

  247. Yamakawa-Kobayashi, K., T. Kobayashi, H. Yanagi, Y. Shimakura, J. Satoh, H. Hamaguchi. 1994. A novel complex mutation in the LDL receptor gene probably caused by the simultaneous occurrence of deletion and insertion in the same region. Human Genet. 93: 625–628.

    Article  CAS  Google Scholar 

  248. Koivisto, P.V., U.M. Koivisto, P.T. Kovanen, H. Gylling, T.A. Miettinen, K. Kontula. 1993. Deletion of exon 15 of the LDL receptor gene is associated with a mild form of familial hypercholesterolemia. Arterioscler. Thromb. 13: 1680–1688.

    Google Scholar 

  249. Koivisto, U–M., L. Hamalainen, M-R. Taskinen, K. Kettunen, and K. Kontula. 1993. Prevalence of familial hypercholesterolemia among young North Karelian patients with coronary heart dissease: A study based on diagnosis by polymerase chain reaction. J. Lipid Res. 34: 269.

    Google Scholar 

  250. Bruin, T., S. Tuzgol, W.J. Mulder, A.E. van den Ende, H. Jansen, M.R. Hayden, and J.J. Kastelein. 1994. A compound heterozygote for lipoprotein lipase deficiency, Val69-Leu and Glyl88-Glu: Correlation between in vitro LPL activity and clinical expression. J. Lipid Res. 35: 438–445.

    Google Scholar 

  251. Wilson, D.E, A. Hata, L.K. Kwong, A. Lingam, J. Shuhua, D.N. Ridinger, C. Yeager, K.C. Kaltenborn, P.H. Iverius, J.M. Lalouel. 1993. Mutations in exon 3 of the lipoprotein lipase gene segregating in a family with hypertriglyceridemia, pancreatitis, and non-insulin-dependent diabetes. J. Clin. Invest. 92: 203–211.

    Google Scholar 

  252. Bijvoet, S.M., T. Bruin, S. Tuzgol, H.D. Bakker, M.R. Hayden, and J.J. Kastelein. 1994. Homozygosity for a mutation in the lipoprotein lipase gene (Gly 139-Ser) causes chylomicronemia in a boy of Spanish descent. Human Genet. 93: 339–343.

    Article  CAS  Google Scholar 

  253. Bruin, T., S. Tuzgol, D.E. van Diermen, N. Hoogerbrugge-van der Linden, J.D. Brunzell, M.R. Hayden, J.J. Kastelein. 1993. Recurrent pancreatitis and chylomicronemia in an extended Dutch kindred is caused by a Gly 154-Ser substitution in lipoprotein lipase. J. Lipid Res. 34: 2109–2119.

    PubMed  CAS  Google Scholar 

  254. Ma, Y., M.S. Liu, D. Ginzinger, J. Frohlich, J.D. Brunzell, and M.R. Hayden. 1993. Gene-environment interaction in the conversion of a mild-to-severe phenotype in a patient homozygous for a, Ser1 Cys mutation in the lipoprotein lipase gene. J. Clin. Invest. 91: 1953–1958.

    Google Scholar 

  255. Haubenwallner, S., G. Horl, N.S. Shachter, E. Presta, S.K. Fried, G. Hofler, G.M. Kostner, J.L. Breslow, and R. Zechner. 1993. A novel missense mutation in the gene for lipoprotein lipase resulting in a highly conservative amino acid substitution (Asp 180-Glu) causes familial chylomicronemia (type I hyperlipoproteinemia). Genomics 18: 392–396.

    Article  PubMed  CAS  Google Scholar 

  256. Tenkanen, H., M–R. Taskinen, M. Antikainen, I. Ulmanen, K. Kontula, and C. Ehnholm. 1994. A novel amino acid substitution (His 183-Gin) in exon 5 of the lipoprotein lipase gene results in loss of catalytic activity: Phenotypic expressin of the mutant gene in a heterozygous state. J. Lipid Res. 35: 220–2283

    Google Scholar 

  257. Reina, M., J.D. Brunzell, and S.S. Deeb. 1992. Molecular basis of familial chylomicronemia: Mutations in the lipoprotein lipase and apolipoprotein C–II genes. J. Lipid Res. 33: 1823–1832.

    Google Scholar 

  258. Ma, Y., M.S. Leu, D. Chitayat, T. Bruin, U. Beisiegel, P. Benlian, L. Foubert, J.L. DeGennes, H. Funke, I. Forsythe. 1994. Recurrent mis–sense mutations at the first and second base of codon Arg243 in human lipoprotein lipase in patients of different ancestries. Human Mutation 3: 52–58.

    Article  PubMed  CAS  Google Scholar 

  259. Ma, Y., T.C. Ooi, M.S. Liu, H. Zhang, R. McPherson, A.L. Edwards, I.J. Forsythe, J. Frohlich, J.D. Brunzell, and M.R. Hayden. 1994. High frequency of mutations in the human lipoprotein lipase gene in pregnancy-induced chylomicronemia: Possible association with apolipoprotein E2 isoform. J. Lipid Res. 35: 1066–1075.

    PubMed  CAS  Google Scholar 

  260. Kobayashi, J., N. Sasaki, J. Tashiro, H. Inadera, Y. Saito, and S. Yoshida. 1993. A missense mutation (Ala-Thr) in exon 7 of the lipoprotein lipase gene in a case iwth type I hyperlipidemia. Biochem. Biophys. Res. Commun. 191: 1046–1054.

    Google Scholar 

  261. Pepe, G., G. Chimienti, F. Resa, V. DiPerma, C. Tarricone, M. Lovecchio, A.M. Colacicco, and A. Capurso. 1994. A new Italian case of lipoprotein lipase deficiency: A Leu Val change resulting in loss of enzyme activity. Biochem. Biophys. Res. Commun. 199: 570–576.

    Google Scholar 

  262. Kozaki, K., T. Gotoda, M. Kawamura, H. Shimano, Y. Yazaki, Y. Ouchi, H. Orimo, and N. Yamada. 1993. Mutational analysis of human lipoprotein lipase by carboxy-terminal truncation. J. Lipid Res. 34: 1765–1772.

    PubMed  CAS  Google Scholar 

  263. Durstenfeld, A., O. Ben-Zeev, K. Reue, G. Stahnke, and M.H. Doolittle. 1994. Molecular characterization of human hepatic lipase deficinecy. In vitro expression of two naturally occurring mutations. Arteriosclerosis & Thrombosis 14: 381–385.

    Google Scholar 

  264. Gotoda, T., N. Yamada, T. Murase, M. Sakuma, N. Murayam, H. Shimano, K. Kozaki, J.J. Albers, Y. Yazaki, and Y. Akanuma. 1991. Differential phenotypic expression by three mutant alleles in familial lecithin:cholesterol acyltransferase deficiency. Lancet 338: 778–781.

    Article  PubMed  CAS  Google Scholar 

  265. Skretting, G., J.P. Blomhoff, J. Solheim, and H. Prydz. 1992. The genetic defect of the original Norwegian lecithin choelsterol acyltransferase deficiency families. FEBS Lett. 309: 307–310.

    Article  PubMed  CAS  Google Scholar 

  266. Klein, H.G., S. Santamarina-Fojo, N. Duverger, M. Clerc, M.F. Dumon, J.J. Albers, S. Marcovina, H.B. Brewer Jr. 1993. Fish eye syndrome: A molecular defect in the lecithin-cholesterol acyltransferase (LCAT) gene associated with normal alpha-LCAT-specific activity. Implications for classification and prognosis. J Clin. Invest. 92: 479–485.

    Google Scholar 

  267. Funke, H., A. von Eckardstein, P.H. Pritchard, A.E. Hornby, H. Wiebusch, C. Motti, M.R. Hayden, C. Dachet, B. Jacotot, U. Gerdes. 1993. Genetic and phenotypic heterogeneity in familial lecithin: Cholesterol acyltransferase (LCAT) deficiency. Six newly identified defective alleles further contribute to the structural heterogeneity in this disease. J. Clin. Invest. 91: 677–683.

    Google Scholar 

  268. Takahashi, K., X.C. Jiang, N. Sakai, S. Yamashita, K. Hirano, H. Bujo, H. Yamazaki, J. Kusunoki, T. Miura, P. Kussie. 1993. A missense mutation in the cholesteryl ester transfer protein gene with possible dominant effects on plasma high density lipoproteins. J. Clin. Invest. 92: 2060–2064.

    Google Scholar 

  269. Gotoda, T., M. Kinoshita, H. Shimano, K. Harada, M. Shimada, J-I. Ohsuga, T. Teramoto, Y. Yazaki, and N. Yamada. 1993. Cholesteryl ester transfer protein deficiency caused by a nonsense mutation detected in the patient’s macrophage mRNA. Biochem. Biophys. Res. Commun. 194: 519–524.

    Google Scholar 

  270. Sharp, D., L. Blinderman, K.A. Combs, B. Klenzie, B. Ricci, K. Wager-Smith, C.M. Gil, C.W. Turck, M.-E. Bouma, D.J. Rader, L.P. Aggerbeck, R.E. Gregg, D.A. Gordon, and J.R. Wetterau. 1993. Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinemia. Nature 365: 65–69.

    Article  PubMed  CAS  Google Scholar 

  271. Groenewegen, W.A., E.S. Krul, and G. Schonfeld. 1993. Apolipoprotein B-52 mutation associated with hypobetalipoproteinemia is compatible with a misaligned pairing deletion mechanism. J. Lipid Res. 34: 971–981.

    PubMed  CAS  Google Scholar 

  272. Young, S.G., C.R. Pullinger, B.R. Zysow, H. Hofinann-Radvani, M.F. Linton, R.V. Farese, Jr., J.F. Terdiman, S.M. Snyder, S.M. Grundy, G.L. Vega. 1993. Four new mutations in the apolipoprotein B gene causing hypobetalipoproteinemia, including two different frameshift mutations that yield truncated apolipoprotein B proteins of identical length. J. Lipid Res. 34: 501–507.

    PubMed  CAS  Google Scholar 

  273. Talmud, P.J., E.S. Krul, M. Pessah, G. Gay, G. Schonfeld, S.E. Humphries, and R. Infante. 1994. Donor splice mutation generates a lipid–associated apolipoprotein B-27.6 in a patient with homozygous hypobetalipoproteinemia. J. Lipid Res. 35: 468–477.

    PubMed  CAS  Google Scholar 

  274. Reina, M., J.D. Brunzell, and S.S. Deeb. 1992. Molecular basis of familial chylomicronemia: Mutations in the lipoprotein lipase and apolipoprotein CII genes. J. Lipid Res. 33: 1823–1832.

    Google Scholar 

  275. Inadera, H., A. Hibino, J. Kobayashi, T. Kanzaki, K. Shirai, S. Yukawa, Y. Saito, and S. Yushida. 1993. A missense mutation (Trp26-Arg) in exon 3 of the apolipoprotein CII gene in a patient with apolipoprotein CII deficiency (apoCII-Wakayama). Biochem. Biophys. Res. Commun. 193: 1174–1183.

    Google Scholar 

  276. Pullinger, C.R., B.R. Zysow, L.L. Hennessy, PH. Frost, M.J. Malloy, and J.R Kane. 1993. Molecular cloning and characteristics of a new apolipoprotein CII mutant identified in three unrelated individuals with hypercholesterolemia and hypertriglyceridemia. Hum. Mol. Genet. 2: 69–74.

    Google Scholar 

  277. Breslow, J.L. 1994. Lipoprotein metabolism and atherosclerosis susceptibility in transgenic mice. Curr.Opin.Lipid 5: 175–184.

    Article  CAS  Google Scholar 

  278. Zhang S.H., R.L. Reddick, J. A. Piedrahita, N. Maeda. 1992. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258: 468–471.

    CAS  Google Scholar 

  279. Reddick R.L., S.H. Zhang, N. Maeda. 1994. Atherosclerosis in mice lacking apoE. Evaluation of lesional development and progression. Arterioscler. Thtvmb. 14: 141–147.

    Google Scholar 

  280. Zhang, S.H. R.L. Reddick, B. Burkey. N. Maeda. 1994. Diet–induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption. J. Clin. Invest. 94: 937–945.

    Google Scholar 

  281. Nakashima Y., A.S. Plump, E.W. Raines, J.L. Breslow, R. Ross. 1994. ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler. Thromb. 14: 133–140.

    Google Scholar 

  282. Simonet W.S., N. Bucay, S.J. Lauer, J.M. Taylor. 1993. Multiple tissue-specific elements control the apolipoprotein E/C–I gene locus in transgenic mice. J. Biol. Chem. 265: 8651–8654.

    Google Scholar 

  283. Aalto-Setala K., E.A. Fisher, X. Chen, T. Chajek-Shaul, T. Hayek, R. Zechner, A. Walsh, R. Ramakrishnan, H.N. Ginsberg, J.L. Breslow. 1992. Mechanism of hypertriglyceridemia in human apoCIII transgenic mice: Diminished VLDL fractional catabolic rate associated with increased apoCIII and reduced apoE on the particles. J. Clin. Invest. 90: 1889–1900.

    Google Scholar 

  284. Schacter N.S., T. Hayek, T. Leff, J.D. Smith, D.W. Rosenberg, A. Walsh, R. Ramakrishnan, I.J. Goldberg, H.N. Ginsberg, J.L. Breslow. 1994. Overexpression of apolipoprotein C-II causes hypertriglyceridemia in transgenic mice. J. Clin. Invest. 93: 1683–1690.

    Google Scholar 

  285. de Silva H.V., S.J. Lauer, J. Wang, W.S. Simonet,K.H. Weisgraber, R.W. Mahley, J.M. Taylor. 1994. Overexpression of human apolipoprotein C-III in transgenic mice results in an accumulation of apolipoprotein B48 remnants that is corrected by excess apolipoprotein E. J. Biol. Chem. 269: 2324.

    Google Scholar 

  286. Maeda N., H. Li, D. Lee, P. Oliver, S.H. Quarfordt, J. Osada. 1994. Targeted disruption of the apolipoprotein C-III gene in mice results in hypotriglyceridemia and protection from postprandial hypertriglyceridemia. J. Biol. Chem. 269: 23610–23616.

    Google Scholar 

  287. van Ree J.H., W.J.A.A. van den Broek, R.R. Frants, M.H. Hofker, L.M. Havekes. 1994. Diet induced hypercholesterolemia in apolipoprotein CI-deficient mice. Circulation 90: 1–135.

    Google Scholar 

  288. Hayek T., N. Azrolan, R.B. Verdery, A. Walsh, T. Chajek-Shaul, L.B. Agellon, A.R. Tall, J.L. Breslow. 1993. Hypertriglyceridemia and cholesteryl ester transfer protein interact to dramatically alter high density lipoprotein levels, particle sizes, and metabolism. J. Clin. Invest. 92: 1143–1152.

    Google Scholar 

  289. Levine, D.M., Parker, T.S., Donnelly, T.M., Walsh, A., Rubin, A.L. 1994. In vivo protein against endotoxin by plasma high density lipoprotein. Pwc. Natl. Acad. Sci. USA 90: 12040–12044.

    Google Scholar 

  290. Chajek-Shaul T., T. Hayek, A. Walsh, J.L. Breslow. 1991. Expression of the human apolipoprotein A-I gene in transgenic mice alters high density lipoprotein (HDL) particle size distribution and diminishes selective uptake of HDL cholesteryl esters. Pwc. Natl. Acad Sci. USA 88: 6731–6735.

    Google Scholar 

  291. Williamson R., D. Lee, J. Hagaman, N. Maeda. 1992. Marked reduction of high density lipoprotein cholesterol in mice genetically modified to lack apolipoprotein A-I. Pwc. Natl. Acad. Sci. USA 89: 7134–7138.

    Google Scholar 

  292. Plump, A.S., T. Hayek, A. Walsh, J.L. Breslow. 1993. Diminished HDL cholesterol ester flux in apoA-I deficient mice. Circulation 88: 2266a.

    Google Scholar 

  293. Li, H., R.L. Reddick, and N. Maeda. 1993. Lack of apoA-I is not associated with increased susceptibility to atherosclerosis in mice. Arteriosclewsis & Thwmbosis 13: 1814–1821.

    Article  CAS  Google Scholar 

  294. Schultz J.R., E.L. Gong, M.R. McCall, A.V. Nichols, S.M. Clift, E.M. Rubin. 1993. Expression of human apolipoprotein A-II and its effect on high density lipoproteins in transgenic mice. J. Biol. Chem. 267: 21630–21636.

    Google Scholar 

  295. Hedrick C.C., W.L. Castellani, C.H. Warden, D.L. Puppione, A.J. Lusis. 1993. Influence of mouse apolipoprotein A-II on plasma lipoproteins in transgenic mice. J. Biol. Chem. 268: 20676–20682.

    Google Scholar 

  296. Schultz J.R., J.G. Verstuyft, E.L. Gong, A.V. Nichols, E.M. Rubin. 1993. Protein composition determines the anti-atherogenic properties of HDL in transgenic mice. Nature 365: 762–764.

    Article  PubMed  CAS  Google Scholar 

  297. Aalto-Setala K., C.L. Bisgaier, A. Ho, K. Kieft, M.G. Traber, H.J. Kayden, R. Ramakrishnan, A. Walsh, A.D. Essenburg, J.L. Breslow. 1994. Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior. J. Clin. Invest. 93: 1776–1786.

    Google Scholar 

  298. Duverger N., G. Tremp, B. Schombert, F. Emmanuel, S. Cune, F. Attenot, N. Touchet, P. Denefle. 1994. Hepatic overexpression of human apolipoprotein A-IV causes hypertriglyceridemia in transgenic mice. Circulation 90: 1–135.

    Google Scholar 

  299. Chiesa G., D.F. Johnson, Z. Yao, T.L. Innerarity, R.W. Mahley, S.G. Young, R.H. Hammer, H.H. Hobbs. 1993. Expression of human apolipoprotein B-100 in transgenic mice. J. Biol. Chem. 268: 23747–23750.

    Google Scholar 

  300. Linton M.F., R.V. Farese Jr., G. Chiesa, D.S. Grass, P. Chin. R.E. Hammer, H.H. Hobbs, S.G. Young. 1993. Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein (a). J. Clin. Invest. 92: 3029–3037.

    Google Scholar 

  301. Callow M.J., L.J. Stoltzfus, R.M. Lawn, E.M. Rubin. 1994. Expression of human apolipoprotein B and assembly of lipoprotein (a) in transgenic mice. Pwc. Natl. Acad. Sci. USA (in press)

    Google Scholar 

  302. Homanics G.E., T.J. Smith, S.H. Zhang, D. Lee, S.G. Young, N. Maeda. 1993. Targeted modification of the apolipoprotein B gene results in hypobetalipoproteinemia and developmental abnormalities in mice. Pwc. Natl. Acad. Sci. USA 90: 2389–2393.

    Google Scholar 

  303. Plump A.S., T.M. Forte, S. Eisenberg, J.L. Breslow. 1993. Atherogenic V-VLDL in the apoE-deficient mouse: Composition, origin, and fate. [Abstract] Circulation 88: A9.

    Google Scholar 

  304. Palinski W., V.A. Ord, A.S. Plump, J.L. Breslow, D. Steinberg, J.L. Witzum. 1994. Apoprotein E-deficient mice are a model of lipoprotein oxidation in atherogenesis: Demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum. Arterioscler. Thwmb. 14: 606–616.

    Google Scholar 

  305. Popko B., J.F. Goodrum, T.W. Bouldin, S.H. Zhang, N. Maeda. 1993. Nerve regeneration occurs in the absence of apolipoprotein E in mice. J. Neuwchem. 60: 1155–1158.

    Article  CAS  Google Scholar 

  306. Paszty C., N. Maeda, J. Verstuyft, E.M. Rubin. 1994. Apolipoprotein A-I transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice. J. Clin. Invest. 94: 899–903.

    Google Scholar 

  307. Chiesa G., H.H. Hobbs, M.L. Koschinsky, R.M. Lawn, S.D. Maika, R.E. Hammer. 1992. Reconstitution of lipoprotein (a) by infusion of human low density lipoprotein into transgenic mice expressing human apolipoprotein (a). J. Biol. Chem. 267: 24369–24374.

    Google Scholar 

  308. Lawn R.M., D.P. Wade, R.E. Hammer, G. Chiesa, J.G. Verstuyft, E.M. Rubin. 1992. Atherogenesis in transgenic mice expressing human apolipoprotein (a). Nature 360: 670–671.

    Article  PubMed  CAS  Google Scholar 

  309. Frazer K. A., G. Narla, J. Zhang, E.M. Rubin. 1994. A 270 Kb yeast artificial chromosome containing apolipoprotein (a) appropriately expresses in transgenic mice. Circulation 90: 1–624.

    Google Scholar 

  310. Hofinann S.L., D.W. Russell, M.S. Brown, J.L. Goldstein, R.E. Hammer. 1988. Overexpression of low density lipoprotein ( LDL) receptor eliminates LDL from plasma in transgenic mice. Science 239: 1277–1281.

    Google Scholar 

  311. Hofinann S.L., D.L. Eaton, M.S. Brown, W.J. McConathy, J.L. Goldstein, R.E. Hammer. 1990. Overexpression of human low density lipoprotein receptors leads to accelerated catabolism of Lp(a) lipoprotein in transgenic mice. J. Cli. Invest. 85: 1542–1547.

    Google Scholar 

  312. Yokode M., R.E. Hammer, S. Ishibashi, M.S. Brown, J.L. Goldstein. 1990. Diet-induced hypercholesterolemia in mice: Prevention by overexpression of LDL receptors. Science 250: 1273–1275.

    Google Scholar 

  313. Ishibashi S., M.S. Brown, J.L. Goldstein, R.D. Gerard, R.E. Hammer, J. Here. 1993. Hypercholesterolemia in low density lipoprotein receptor knockout mice in its reversal by adenovirus-mediated gene delivery. J. Clin. Invest. 92: 883–893.

    Google Scholar 

  314. Ishibashi S., Herz J., Maeda N., Golstein J.L., Brown M.S. 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.

    Google Scholar 

  315. Herz J., D.E. Clouthier, R.E. Hammer. 1992. LDL receptor-related protein internalizes and degrades uPA-PA-1 complexes and is essential for embryo implantation. Cell.71 (3):411 –421.

    Google Scholar 

  316. Shimada M., H. Shimano, T. Gotoda, K. Yamomoto, M. Kawamura, T. Inaba, Y. Yazaki, N. Yamada. 1993. Overexpression of human lipoprotein lipase in transgenic mice. J. Biol. Chem. 268:17924– 17929.

    Google Scholar 

  317. Fan J., J. Wang, Z-S. Ji, D. Sanan, Q. Dang, A. Bensadoun, R.W. Mahley, J.M. Taylor. 1994. Transgenic rabbits overexpressing human hepatic lipase have reduced levels of high density lipoproteins and intermediate density lipoproteins and diminished responses to dietary cholesterol. Circulation 90: 1–289.

    Google Scholar 

  318. Berard A., R.D. Shamburek, B. Vaisman, S. Meyn, M. Kindt, J. Albers, S. Santamarina-Fojo, H.B. Brewer Jr. 1994. Differential dietary response of mice overexpressing hLCAT. Circulation 90: 1–82.

    Google Scholar 

  319. Francone O.L., E.L. Gong, P. Cooper, C.J. Fielding, E.M. Rubin. 1994. Expression of human lecithin:cholesterol acyltransferase in transgenic mice: Studies on substrate specificity. Circulation 90: 1–82.

    Google Scholar 

  320. Agellon L.B., A. Walsh, T. Hayek, P. Moulin, X.C. Jiang, S.A. Shelanski, J.L. Breslow, A.R. Tall. 1991. Reduced high density lipoprotein cholesterol in human cholesterol ester transfer protein transgenic mice. J. Biol. Chem. 266: 10796–10801.

    Google Scholar 

  321. Marotti K.R., C.K. Castle, R.W. Murray, E.F. Rehberg, H.G. Polites, G.W. Melchior. 1992. The role of cholesteiyl ester transfer protein in primate apolipoprotein A-I metabolism. Insights from studies with transgenic mice. Arterioscler. Thromb. 12: 736–744

    Google Scholar 

  322. Jiang X.C., L. Masucci-Magoulas, J. Mar, M. Lin, A. Walsh, J.L. Breslow, A. Tall. 1993. Down-regulation of mRNA for the low density lipoprotein receptor in transgenic mice containing the gene for human cholesteryl ester transfer protein. Mechanism to explain accumulation of lipoprotein B particles. J. Biol. Chem. 268: 27406–27412.

    Google Scholar 

  323. Zhong S., I.J. Goldberg, C. Bruce, E. Rubin, J.L. Breslow, A. Tall. 1994. Human apoA-II inhibits the hydrolysis of HDL triglyceride and the decrease of HDL size induced by hypertriglyceridemia and CETP in transgenic mice. Circulation 90: 1–81.

    Google Scholar 

  324. Grass D.S., U. Saini, R.H. Felkner, S.G. Young, R.E. Wallace, T.D. Yeck, M.E. Swanson. 1994. Transgenic mice expressing human apoB and human cholesteryl ester transfer protein have a lipoprotein-cholesterol profile similar to that of normolipidemic humans. Circulation 90: 1–134

    Google Scholar 

  325. Fazio S., K.R., Marotti, Y-L. Lee, C.K. Castle, G.W. Melchior, S.C. Rail, Jr. 1994. Co-expression of cholesteryl ester transfer protein and defective apolipoprotein E in transgenic mice alaters plasma cholesterol distribution. J. Biol. Chem. 269: 32368–32372.

    Google Scholar 

  326. Bockxmeer M. V., C.D. Mamotte, F.R. Gibbons and R.R. Taylor. 1993. Apolipoprotein E4 homozygosity is an important determinant of restenosis after coronary angioplasty. Circulation 88: 519.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Molecular Genetics, Boston University Medical Center, USA

    Vassilis I. Zannis, Maria Laccotripe, Savvas C. Makrides & Eleni Zanni

  2. Institute of Molecular Biology and Biotechnology of Crete, The University of Crete Medical School, Greece

    Vassilis I. Zannis & Dimitris Kardassis

Authors
  1. Vassilis I. Zannis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Laccotripe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Savvas C. Makrides
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dimitris Kardassis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eleni Zanni
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medical College of Georgia, Augusta, Georgia, USA

    John D. Catravas

  2. Boston University School of Medicine, Boston, Massachusetts, USA

    Allan D. Callow

  3. T Cell Sciences, Inc., Needham, Massachusetts, USA

    Una S. Ryan

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Plenum Press, New York

About this chapter

Cite this chapter

Zannis, V.I., Laccotripe, M., Makrides, S.C., Kardassis, D., Zanni, E. (1996). Genetic Factors Contributing to Cardiovascular Disease that may affect Endothelial Structure and Function: The Role of Proteins involved in Lipoprotein Transport. In: Catravas, J.D., Callow, A.D., Ryan, U.S. (eds) Vascular Endothelium. NATO ASI Series, vol 281. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0355-8_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-0355-8_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-8013-9

  • Online ISBN: 978-1-4613-0355-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation