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High-Density Lipoprotein Metabolism

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Atlas of Atherosclerosis and Metabolic Syndrome

Abstract

High-density lipoprotein (HDL) cholesterol (HDL-C) concentrations are inversely associated with coronary heart disease (CHD) in humans [1,2]. The initial descriptions of this inverse relationship in the early 1950s [3–5] were “rediscovered” in the 1970s [6–9]. The major mechanism proposed for the protective effect of HDL is reverse cholesterol transport, a process in which excess cholesterol from peripheral cells is transported back to the liver for removal from the body [10]. The higher the plasma levels of HDL, the more efficient is the transport to the liver of excess cholesterol from peripheral cells.

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References

  1. Gordon DJ, Probstfield JL, Garrison RJ, et al: High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation 1989, 79:8–15.

    PubMed  Google Scholar 

  2. Gordon DJ, Rifkind BM: High-density lipoprotein: the clinical implications of recent studies. N Engl J Med 1989, 321:1311–1316.

    Article  PubMed  Google Scholar 

  3. Gofman JW, Lindgren F, Elliot H, et al: The role of lipids and lipoproteins in atherosclerosis. Science 1950, 111:166–186.

    Article  PubMed  Google Scholar 

  4. Gofman JW, deLalla O, Glazier F, et al: The serum lipid transport system in health, metabolic disorders, atherosclerosis, and coronary artery disease. Plasma 1954, 2:413–484.

    Google Scholar 

  5. Barr DP, Russ EM, Eder HA: Protein-lipid relationship in human plasma. II. In atherosclerosis and related conditions. Am J Med 1951, 11:480–493.

    Article  PubMed  Google Scholar 

  6. Miller GJ, Miller NE: Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet 1975, 1:16–19.

    Article  PubMed  Google Scholar 

  7. Rhoads GG, Gulbrandsen CL, Kagan A: Serum lipoproteins and coronary heart disease in a population study of Hawaii Japanese men. N Engl J Med 1976, 294:293–298.

    Article  PubMed  Google Scholar 

  8. Gordon T, Castelli WP, Hjortland MC, et al: High density lipoprotein as a protective factor against coronary heart disease. The Framingham study. Am J Med 1977, 62:707–714.

    Article  PubMed  Google Scholar 

  9. Miller NE, Thelle DS, Forde OH, Mjos OD: The Tromso heart-study: high-density lipoproteins and coronary heart-disease: a prospective case-control study. Lancet 1977, 1:965–968.

    Article  PubMed  Google Scholar 

  10. Glomset JA, Janssen ET, Kennedy R, et al: Role of plasma lecithin:cholesterol acyltransferase in the metabolism of high density lipoproteins. J Lipid Res 1966, 7:638–648.

    PubMed  Google Scholar 

  11. Brewer HB Jr, Santamarina-Fojo S, Hoeg JM: The molecular biology of the human plasma apolipoproteinemia, lipoprotein receptors, and lipoprotein lipase. In Primary Hyperlipoproteinemias. Edited by Steiner G, Shafrir E. New York: McGraw-Hill; 1990:43–74.

    Google Scholar 

  12. Breslow JL: Familial disorders of high-density lipoprotein metabolism. In The Metabolic and Molecular Bases of Inherited Disease. Edited by Scriver CR, Beaudet AL, Sly WS, et al. New York: McGraw-Hill; 1995:2031–2052.

    Google Scholar 

  13. Menotti A, Keys A, Aravanis C, et al: Seven Countries Study. First 20-year mortality data in 12 cohorts of six countries. Ann Med 1989, 21:175–179.

    Article  PubMed  Google Scholar 

  14. Keys A: High density lipoprotein cholesterol and longevity. J Epidemiol Community Health 1987, 42:60–65.

    Article  Google Scholar 

  15. Barter P, Gotto AM, LaRosa JC, et al: Treating to New Targets Investigators. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007, 357:1301–1310.

    Article  PubMed  Google Scholar 

  16. Barter PJ, Baker PW, Rye KA: Effect of high-density lipoproteins on the expression of adhesion molecules in endothelial cells. Curr Opin Lipidol 2002,13:285–288.

    Article  PubMed  Google Scholar 

  17. Mineo C, Shaul PW: Role of high-density lipoprotein and scavenger receptor B type I in the promotion of endothelial repair. Trends Cardiovasc Med 2007, 17:156–161.

    Article  PubMed  Google Scholar 

  18. Marathe GK, Zimmerman GA, McIntyre TM: Platelet-activating factor acetylhydrolase, and not paraoxonase-1, is the oxidized phospholipid hydrolase of high density lipoprotein particles. J Biol Chem 2002, 278:3937–3947.

    Article  PubMed  Google Scholar 

  19. Parthasarathy S, Fong LG, Otero D, Steinberg D: Recognition of solubilized apoproteins from delipidated, oxidized low density lipoprotein (LDL) by the acetyl-LDL receptor. Proc Natl Acad Sci U S A 1987, 84:537–540.

    Article  PubMed  Google Scholar 

  20. Parthasarathy S, Barnett J, Fong LG: High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein. Biochim Biophys Acta 1990, 1044:275–283.

    PubMed  Google Scholar 

  21. Brewer HB Jr, Santamarina-Fojo S, Hoeg JM: Molecular biology of the lipoproteins and the apolipoproteins and their role in atherosclerosis. In Molecular Basis of Cardiology. Edited by Roberts R. Boston: Blackwell Scientific; 1992:415–441.

    Google Scholar 

  22. Segrest JP, Jones MK, De Loof H, et al: The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function. J Lipid Res 1992, 33:141–166.

    PubMed  Google Scholar 

  23. Segrest JP, Garber DW, Brouillette CG, et al: The amphipathic alpha helix: a multifunctional structural motif in plasma apolipoproteins. Adv Protein Chem 1994, 45:303–369.

    Article  PubMed  Google Scholar 

  24. Brewer HB Jr, Remaley AT, Neufeld EB, et al: Regulation of plasma high-density lipoprotein levels by the ABCA1 transporter and the emerging role of high-density lipoproteins in the treatment of cardiovascular disease. Arterioscler Thromb Vasc Biol 2004, 24: 1755–1760.

    Article  PubMed  Google Scholar 

  25. Acton S, Rigotti A, Landschulz KT, et al: Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 1996, 271:518–520.

    Article  PubMed  Google Scholar 

  26. Murao K, Terpstra V, Green SR et al: Characterization of CLA-1, a human homologue of rodent scavenger receptor BI, as a receptor for high density lipoprotein and apoptotic thymocytes. J Biol Chem 1997, 272:17551–17557.

    Article  PubMed  Google Scholar 

  27. Landschulz KT, Pathak RK, Rigotti A, et al: Regulation of scavenger receptor, class B, type I, a high density lipoprotein receptor, in liver and steroidogenic tissues of the rat. J Clin Invest 1996, 98:984–995.

    Article  PubMed  Google Scholar 

  28. Tall AR: Metabolic and genetic control of HDL cholesterol levels. J Intern Med 1992, 231:661–668.

    Article  PubMed  Google Scholar 

  29. Assman G, von Eckardstein A, Brewer HB Jr: The Metabolic and Molecular Basis of Inherited Disease, edn 8. Edited by Scriver CR, Beaudet AL, Sly WS, et al. New York: McGraw Hill; 2001: 2937–2980.

    Google Scholar 

  30. Scanu AM, Fless GM: Lipoprotein (a). Heterogeneity and biological relevance. J Clin Invest 1990, 85:1709–1715.

    Article  PubMed  Google Scholar 

  31. Rader DJ, Schaefer JR, Lohse P, et al: Increased production of apolipoprotein A-I associated with elevated plasma levels of high-density lipoproteins, apolipoprotein A-I, and lipoprotein A-I in a patient with familial hyperalphalipoproteinemia. Metabolism 1993, 42: 1429–1434.

    Article  PubMed  Google Scholar 

  32. Ikewaki K, Rader DJ, Sakamoto T, et al: Delayed catabolism of high density lipoprotein apolipoproteins A-I and A-II in human cholesteryl ester transfer protein deficiency. J Clin Invest 1993, 92: 1650–1658.

    Article  PubMed  Google Scholar 

  33. Tall AR: Plasma cholesteryl ester transfer protein. J Lipid Res 1993, 34:1255–1274.

    PubMed  Google Scholar 

  34. Yamashita S, Ishigami M, Arai T, et al: Very high density lipoproteins induced by plasma cholesteryl ester transfer protein (CETP) have a potent antiatherogenic function. Ann N Y Acad Sci 1995, 748:606–608.

    Article  PubMed  Google Scholar 

  35. Tall AR: An overview of reverse cholesterol transport. Eur Heart J 1998, 19:A31–A35.

    PubMed  Google Scholar 

  36. Ng DS, Leiter LA, Vezina C, et al: Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. J Clin Invest 1994, 93:223–229.

    Article  PubMed  Google Scholar 

  37. Lackner KJ, Dieplinger H, Nowicka G, et al: High density lipoprotein deficiency with xanthomas. A defect in reverse cholesterol transport caused by a point mutation in the apolipoprotein A-I gene. J Clin Invest 1993, 92:2262–2273.

    Article  PubMed  Google Scholar 

  38. Bekaert ED, Alaupovic P, Knight-Gibson CS, et al: Characterization of apo A- and apo B-containing lipoprotein particles in a variant of familial apo A-I deficiency with planar xanthoma: the metabolic significance of LP-A-II particles. J Lipid Res 1991, 32:1587–1599.

    PubMed  Google Scholar 

  39. Sherman JL, Citrin C, Johns T, et al: Erdheim-Chester disease: ­computed tomography in two cases. Am J Neuroradiol 1985, 6:444–445.

    PubMed  Google Scholar 

  40. Ordovas JM, Cassidy DK, Civeira F, et al: 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 1989, 264:16339–16342.

    PubMed  Google Scholar 

  41. Genest JJ Jr, Martin-Munley SS, McNamara JR, et al: Familial lipoprotein disorders in patients with premature coronary artery disease. Circulation 1992, 85:2025–2033.

    PubMed  Google Scholar 

  42. Schaefer EJ, Blum CB, Levy RI, et al: Metabolism of high-density lipoprotein apolipoproteins in Tangier disease. N Engl J Med 1978, 299:905–910.

    Article  PubMed  Google Scholar 

  43. Schaefer EJ, Zech LA, Schwartz DE, Brewer H Jr: Coronary heart disease prevalence and other clinical features in familial high-density lipoprotein deficiency (Tangier disease). Ann Intern Med 1980, 93:261–266.

    PubMed  Google Scholar 

  44. Serfaty-Lacrosniere C, Civeira F, Lanzberg A, et al: Homozygous Tangier disease and cardiovascular disease. Atherosclerosis 1994, 107:85–98.

    Article  PubMed  Google Scholar 

  45. Rader DJ, Ikewaki K, Duverger N, et al: Very low high-density lipoproteins without coronary atherosclerosis. Lancet 1993, 342:1455–1458.

    Article  PubMed  Google Scholar 

  46. Krauss RM: Regulation of high density lipoprotein levels. Med Clin North Am 1982, 66:403–430.

    PubMed  Google Scholar 

  47. Rubins HB, Robins SJ, Collins D, et al: Gemfibrozil for the secondary prevention of coronary artery disease in men with low levels of ­high-density lipoprotein cholesterol. Veterans Affairs High Density Lipoprotein Cholesterol Intervention Study Group. N Engl J Med 1999, 341:410–418.

    Article  PubMed  Google Scholar 

  48. Brewer HB Jr: High-density lipoproteins: a new potential therapeutic target for the prevention of cardiovascular disease. Arterioscler Thromb Vasc Biol 2004, 24:387–391.

    Article  PubMed  Google Scholar 

  49. Brewer HB Jr: Increasing HDL cholesterol levels. N Engl J Med 2004, 350:1491–1494.

    Article  PubMed  Google Scholar 

  50. Nissen SE, Tsunoda T, Tuzcu EM, et al: Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 2003, 290:2292–2300.

    Article  PubMed  Google Scholar 

  51. Waksman R, Kent K, Pichard M, et al: A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated HDL plasma infusions in patients with acute coronary syndrome. Circulation 2008, 118:S371.

    Google Scholar 

  52. Barter PJ, Caulfield M, Eriksson M, et al: Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007, 357:2109–2122.

    Article  PubMed  Google Scholar 

  53. Cannon CP, Dansky HM, Davidson M, et al: Design of the DEFINE trial: determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib. Am Heart J 2009, 158:513–519.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Lipoprotein and Atherosclerosis Research, Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington, DC, USA

    H. Bryan Brewer Jr (Director, Washington Cardiovascular Associates, Senior Research Consultant)

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  1. H. Bryan Brewer Jr
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Editors and Affiliations

  1. Southwestern Medical Center, Dept. Clinical Nutrition &, University of Texas, Harry Hines Blvd. 5323, Dallas, 75390, Texas, USA

    Scott M. Grundy

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Brewer, H.B. (2011). High-Density Lipoprotein Metabolism. In: Grundy, S. (eds) Atlas of Atherosclerosis and Metabolic Syndrome. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5839-6_5

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  • DOI: https://doi.org/10.1007/978-1-4419-5839-6_5

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  • Publisher Name: Springer, New York, NY

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