Skip to main content
SpringerLink
Log in

The concept of apolipoprotein-defined lipoprotein families and its clinical significance

  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Classification of plasma lipoproteins on the basis of apolipoprotein (apo) composition recognizes two lipoprotein (Lp) classes, one of which is characterized by apoA-I and the other by apoB as major protein constituents. The former lipoprotein class consists of three major subclasses referred to (according to their apolipoprotein constituents) as Lp-A-I, Lp-A-I:A-II, and Lp-A-II, and the latter one of five subclasses called Lp-B, Lp-B:E, Lp-B:C, Lp-B:C:E, and Lp-A-II:B:C:D:E. As polydisperse systems of particles, the apoA-I-containing lipoproteins overlap in high-density segments and apoB-containing lipoproteins in low-density segments of the density gradient. Each subclass is characterized by a specific chemical composition and metabolic property. Normolipidemia and dyslipoproteinemias are characterized by quantitative rather than qualitative differences in the levels of apoA- and apoB-containing subclasses. Furthermore, apoA-containing subclasses seem to differ with respect to their relative antiatherogenic capacities, and apoB-containing subclasses regarding their relative atherogenic potentials. Whereas Lp-A-I may have a greater antiatherogenic capacity than other apoA-containing subclasses, the cholesterol-enriched Lp-B:C appears to be the most atherogenic subclass among apoB-containing lipoprotein families. The use of pharmacologic and/or dietary interventions to treat dyslipoproteinemias has already shown that these therapeutic modalities may affect selectively individual apolipoprotein-defined lipoproteins, and thus allow the selection of individualized treatments targeted at decreasing harmful and/or increasing beneficial lipoprotein subclasses.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gofman JW, De Lalla O, Glazier F, et al.: The serum lipoprotein transport system in health, metabolic disorders, atherosclerosis, and coronary heart disease. Plasma 1954, 2:413–484.

    Google Scholar 

  2. Jones HB, Gofman JW, Lindgren FT, et al.: Lipoproteins in atherosclerosis. Am J Med 1951, 11:358–380.

    Article  PubMed  CAS  Google Scholar 

  3. Nichols AV: Human serum lipoproteins and their interrelationships. Adv Biol Med Phys 1967, 11:109–158.

    PubMed  CAS  Google Scholar 

  4. Fredrickson DS, Levy RI, Lees RS: Fat transport in lipoproteins: an integrated approach to mechanism and disorders. N Engl J Med 1967, 276:32–281.

    Google Scholar 

  5. Ewing AM, Freeman NK, Lindgren FT: The analysis of human serum lipoprotein distributions. Adv Lipid Res 1965, 3:25–61.

    PubMed  CAS  Google Scholar 

  6. Nestel P, Billington T, Tada N, et al.: Heterogeneity of very-low-density lipoprotein metabolism in hyperlipidemic subjects. Metabolism 1983, 32:810–817.

    Article  PubMed  CAS  Google Scholar 

  7. Nestel P: High-density lipoprotein turnover. Am Heart J 1987, 113:518–521.

    Article  PubMed  CAS  Google Scholar 

  8. Packard CJ, Shepherd J: Lipoprotein heterogeneity and apolipoprotein B metabolism. Arterioscler Thromb Vasc Biol 1997, 17:3542–3556.

    PubMed  CAS  Google Scholar 

  9. Alaupovic P: Conceptual development of the classification systems of plasma lipoproteins. Protides Biol Fluids Proc Colloq 1972, 19:9–19.

    Google Scholar 

  10. Osborne JC Jr, Brewer HB Jr: The plasma lipoproteins. Adv Protein Chem 1977, 31:253–337.

    Article  PubMed  CAS  Google Scholar 

  11. Alaupovic P: Apolipoprotein composition as the basis for classifying plasma lipoproteins. Characterization of ApoA- and ApoB-containing lipoprotein families. Prog Lipid Res 1991, 30:105–138.

    Article  PubMed  CAS  Google Scholar 

  12. Fredrickson DS: Phenotyping. On reaching base camp (1950–1975). Circulation 1993, 87(suppl II):1–15.

    Google Scholar 

  13. Alaupovic P, Lee DM, McConathy WJ: Studies on the composition and structure of plasma lipoproteins. Distribution of lipoprotein families in major density classes of normal human plasma lipoproteins. Biochim Biophys Acta 1972, 260:689–707.

    PubMed  CAS  Google Scholar 

  14. Lee DM, Alaupovic P: Composition and concentration of apolipoproteins in very-low- and low-density lipoproteins of normal human plasma. Atherosclerosis 1974, 19:501–520.

    PubMed  CAS  Google Scholar 

  15. Lee DM, Alaupovic P: Apolipoproteins B, C-III and E in two major subpopulations of low-density lipoproteins. Biochim Biophys Acta 1986, 879:126–133.

    PubMed  CAS  Google Scholar 

  16. Cheung MC, Albers JJ: Distribution of cholesterol and apolipoprotein A-I and A-II in human high density lipoprotein subtractions separated by NaCl equilibrium gradient centrifugation: evidence for HDL subpopulations with differing A-I/A-II molar ratios. J Lipid Res 1979, 20:200–207.

    PubMed  CAS  Google Scholar 

  17. Alaupovic P: Significance of apolipoproteins for structure, function and classification of plasma lipoproteins. In Methods in Enzymology. Plasma Lipoproteins, Part C, Quantitation. Edited by Bradley WA, Gianturco SH, Segrest JP. San Diego: Academic Press; 1996.

    Google Scholar 

  18. Bekaert ED, Alaupovic P, Knight-Gibson C, et al.: Composition of plasma ApoA-I-containing lipoprotein particles in children and adults. Pediatr Res 1991, 29:315–321.

    Article  PubMed  CAS  Google Scholar 

  19. Ohta T, Ikeda Y, Nakamura R, et al.: Lipoprotein-containing apolipoprotein A-I-sex-related quantitative and qualitative changes in this lipoprotein subspecies after ingestion of fat. Am J Clin Nutr 1992, 56:404–409.

    PubMed  CAS  Google Scholar 

  20. Rader DJ, Castro G, Zech LA, et al.: In vivo metabolism of apolipoprotein A-I on high density lipoprotein particles LpA-I and LpA-I:A-II. J Lipid Res 1991, 32:1849–1859.

    PubMed  CAS  Google Scholar 

  21. Hannuksela ML, Brousseau ME, Meyn SM, et al.: In vivo metabolism of apolipoprotein E within the HDL subpopulations LpE, LpE:A-I, LpE:A-II and LpE:A-I:A-II. Atherosclerosis 2002, 165:205–220.

    Article  PubMed  CAS  Google Scholar 

  22. Fielding CJ, Fielding PE: Evidence for a lipoprotein carrier in human plasma catalyzing sterol efflux from cultured fibroblasts and its relationship to lecithin:cholesterol acyltransferase. Proc Natl Acad Sci USA 1981, 78:3911–3914.

    Article  PubMed  CAS  Google Scholar 

  23. Barkia A, Puchois P, Ghalim N, et al.: Differential role of apolipoprotein A1-containing particles in cholesterol efflux from adipose cells. Atherosclerosis 1991, 87:135–146.

    Article  PubMed  CAS  Google Scholar 

  24. Cheung MC, Wolf AC, Lum KD, et al.: Distribution and localization of lecithin:cholesterol acyltransferase and cholesteryl ester transfer activity in A-I-containing lipoproteins. J Lipid Res 1986, 27:1135–1144.

    PubMed  CAS  Google Scholar 

  25. Rinninger F, Kaiser T, Windler E, et al.: Selective uptake of cholesteryl esters from high-density lipoprotein-derived LpA-I and LpA-I:A-II particles by hepatic cells in culture. Biochim Biophys Acta 1998, 1393:277–291.

    PubMed  CAS  Google Scholar 

  26. Alaupovic P: David Rubenstein Memorial Lecture: the biochemical and clinical significance of the interrelationship between very low density and high density lipoproteins. Can J Biochem 1981, 59:565–579.

    Article  PubMed  CAS  Google Scholar 

  27. James RW, Pometta D: Postprandial lipemia differentially influences high density lipoprotein subpopulations LpAI and LpAI,AII. J Lipid Res 1994, 35:1583–1591.

    PubMed  CAS  Google Scholar 

  28. Dashti N, Alaupovic P, Knight-Gibson C, et al.: Identification and partial characterization of discrete apolipoprotein B-containing lipoprotein particles produced by human hepatoma cell line HepG2. Biochemistry 1987, 26:4837–4846.

    Article  PubMed  CAS  Google Scholar 

  29. Alaupovic P, Knight-Gibson C, Wang CS, et al.: Isolation and characterization of an apoA-II-containing lipoprotein (LP-A-II:B complex) from plasma very low density lipoproteins of patients with Tangier disease and type V hyperlipoproteinemia. J Lipid Res 1991, 32:9–19.

    PubMed  CAS  Google Scholar 

  30. Koren E, Alaupovic P, Lee DM, et al.: Selective isolation of human plasma low-density lipoprotein particles containing apolipoproteins B and E by use of a monoclonal antibody to apolipoprotein B. Biochemistry 1987, 26:2734–2740.

    Article  PubMed  CAS  Google Scholar 

  31. Agnani G, Bard JM, Candelier L, et al.: Interaction of LpB, LpB:E, LpB:C-III, and LpB:C-III:E lipoproteins with the low density lipoprotein receptor of HeLa cells. Arterioscler Thromb 1991, 11:1021–1029.

    PubMed  CAS  Google Scholar 

  32. Clavey V, Lestavel-Delattre S, Copin C, et al.: Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E. Arterioscler Thromb Vasc Biol 1995, 15:963–971.

    PubMed  CAS  Google Scholar 

  33. Koren E, Koscec M, Corder C, et al.: Differential atherogenicity of complex apoB-containing lipoprotein particles. Atherosclerosis 1994, 109:217–218.

    Article  Google Scholar 

  34. Wallace RB, Anderson RA: Blood lipids, lipid-related measures and the risk of atherosclerotic cardiovascular disease. Epidemiol Rev 1987, 9:95–119.

    PubMed  CAS  Google Scholar 

  35. März W, Trommlitz M, Gross W: Differential turbidimetric assay for subpopulations of lipoproteins containing apolipoprotein A-I. J Clin Chem Clin Biochem 1988, 26:573–578.

    PubMed  Google Scholar 

  36. Alaupovic P, Tavella M, Fesmire J: Separation and identification of apoB-containing lipoprotein particles in normolipidemic subjects and patients with hyperlipoproteinemias. Adv Exp Med Biol 1987, 210:7–14.

    PubMed  CAS  Google Scholar 

  37. Alaupovic P, Koren E: Immunoaffinity chromatography of plasma lipoprotein particles. In Analyses of Fats, Oils and Lipoproteins. Edited by Perkins EG. Champaign, IL: American Oil Chemists’ Society; 1991.

    Google Scholar 

  38. Koren E, Puchois P, Alaupovic P, et al.: Quantification of two different types of apolipoprotein A-I containing lipoprotein particles in plasma by enzyme-linked differential-antibody immunosorbent assay. Clin Chem 1987, 33:38–43.

    PubMed  CAS  Google Scholar 

  39. Parra HJ, Mezdour H, Ghalim N, et al.: Differential electroimmunoassay of human LpA-I lipoprotein particles on ready-to-use plates. Clin Chem 1990, 36:1431–1435.

    PubMed  CAS  Google Scholar 

  40. Alaupovic P, Fesmire JD, Hunninghake D, et al.: The effect of aggressive and moderate lowering of LDL-cholesterol and low dose anticoagulation on plasma lipids, apolipoproteins and lipoprotein families in post coronary artery bypass graft trial. Atherosclerosis 1999, 146:369–379.

    Article  PubMed  CAS  Google Scholar 

  41. Puchois P, Kandoussi A, Fievet P, et al.: Apolipoprotein A-I containing lipoproteins in coronary artery disease. Atherosclerosis 1987, 68:35–40.

    Article  PubMed  CAS  Google Scholar 

  42. Coste-Burel M, Mainard F, Chivot L, et al.: Study of lipoprotein particles LpAI and LpAI:AII in patients before coronary bypass surgery. Clin Chem 1990, 36:1889–1891.

    PubMed  CAS  Google Scholar 

  43. Montali A, Vega GL, Grundy SM: Concentrations of apolipoprotein A-I-containing particles in patients with hypoalphalipoproteinemia. Arterioscler Thromb 1994, 14:511–517.

    PubMed  CAS  Google Scholar 

  44. Cheung MC, Brown BG, Wolf AC, et al.: Altered particle size distribution of apolipoprotein A-I-containing lipoproteins in subjects with coronary artery disease. J Lipid Res 1991, 32:383–394.

    PubMed  CAS  Google Scholar 

  45. O’Brien T, Nguyen TT, Hallaway BJ, et al.: The role of lipoprotein A-I and lipoprotein A-I/A-II in predicting coronary artery disease. Arterioscler Thromb Vasc Biol 1995, 15:228–231.

    PubMed  CAS  Google Scholar 

  46. Duverger N, Rader D, Brewer HB Jr: Distribution of subclasses of HDL containing ApoA-I without ApoA-II (LpA-I) in normolipidemic men and women. Arterioscler Thromb 1994, 14:1594–1599.

    PubMed  CAS  Google Scholar 

  47. Alaupovic P, Mack WJ, Knight-Gibson C, et al.: The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial. Arterioscler Thromb Vasc Biol 1997, 17:715–722.

    PubMed  CAS  Google Scholar 

  48. Brown BG, Zhao XQ, Chait A, et al.: Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001, 345:1583–1592.

    Article  PubMed  CAS  Google Scholar 

  49. Asztalos BF, Batista M, Horvath KV, et al.: Change in alpha1 HDL concentration predicts progression in coronary artery stenosis. Arterioscler Thromb Vasc Biol 2003, 23:847–852.

    Article  PubMed  CAS  Google Scholar 

  50. Luc G, Bard JM, Ferrières J, et al.: Value of HDL cholesterol, apolipoprotein A-I, lipoprotein A-I, and lipoprotein A-I/A-II in prediction of coronary heart disease—The PRIME Study. Arterioscler Thromb Vasc Biol 2002, 22:1155–1161.

    Article  PubMed  CAS  Google Scholar 

  51. Nordestgaard BG, Tybaerg-Hansen A: IDL, VLDL, chylomicrons and atherosclerosis. Eur J Epidemiol 1992, 8:92–98.

    Article  PubMed  Google Scholar 

  52. Gould AL, Rossouw JE, Santanello NC, et al.: Cholesterol reduction yields clinical benefit: impact of statin trials. Circulation 1998, 97:946–952.

    PubMed  CAS  Google Scholar 

  53. Alaupovic P: On the atherogenicity of triglyceride-rich lipoproteins and a novel marker for the assessment of their atherogenic potentials. OCL 2002, 9:220–226.

    CAS  Google Scholar 

  54. Hokanson JE, Austin MA: Plasma triglyceride levels is an independent risk factor for cardiovascular disease: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996, 3:213–219.

    Article  PubMed  CAS  Google Scholar 

  55. Cullen P: Evidence that triglycerides are an independent coronary heart disease risk factor. Am J Cardiol 2000, 86:943–949.

    Article  PubMed  CAS  Google Scholar 

  56. Ginsberg HN: New perspectives in atherogenesis. Role of abnormal triglyceride-rich lipoprotein metabolism. Circulation 2002, 106:2137–2142.

    Article  PubMed  Google Scholar 

  57. Zilversmit DB: Atherogenic nature of triglycerides, postprandial lipidemia, and triglyceride-rich remnant lipoproteins. Clin Chem 1995, 41:153–158.

    PubMed  CAS  Google Scholar 

  58. Blankenhorn DH, Alaupovic P, Wickham E, et al.: Prediction of angiographic change in native human coronary arteries and aortocoronary bypass grafts—lipid and nonlipid factors. Circulation 1990, 81:470–476.

    PubMed  CAS  Google Scholar 

  59. Alaupovic P, Blankenhorn DH: Identification of potentially atherogenic lipoprotein particles. In Molecular Biology of Atherosclerosis, Proceedings of the 57th European Atherosclerosis Meeting. Edited by Halpern MJ. London: John Libbey & Company; 1992.

    Google Scholar 

  60. Sacks FM, Alaupovic P, Moye LA, et al.: VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the cholesterol and recurrent events (CARE) Trial. Circulation 2000, 102:1886–1892.

    PubMed  CAS  Google Scholar 

  61. Koren E, Corder C, Mueller G, et al.: Triglyceride enriched lipoprotein particles correlate with the severity of coronary artery disease. Atherosclerosis 1996, 122:105–115.

    Article  PubMed  CAS  Google Scholar 

  62. Alaupovic P, Bard JM, Tavella M, et al.: Identification of apoB-containing lipoprotein families in NIDDM. Diabetes 1992, 41(suppl 2):18–25.

    PubMed  Google Scholar 

  63. Gervaise N, Garrigue MA, Lasfargues G, et al.: Triglycerides, apoC3 and LpB:C3 and cardiovascular risk in type II diabetes. Diabetologia 2000, 43:703–708.

    Article  PubMed  CAS  Google Scholar 

  64. Lee SJ, Campos H, Moye LA, et al.: LDL containing apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients. Arterioscler Thromb Vasc Biol 2003, 23:853–858.

    Article  PubMed  CAS  Google Scholar 

  65. Atmeh RG, Shepherd J, Packard CJ: Subpopulations of apolipoprotein A-I in human high-density lipoproteins. Their metabolic profiles and response to drug therapy. Biochim Biophys Acta 1983, 751:175–188.

    PubMed  CAS  Google Scholar 

  66. Bard JM, Parra HJ, Camare R, et al.: A multicenter comparison of the effects of simvastatin and fenofibrate therapy in severe primary hypercholesterolemia, with particular emphasis on lipoproteins defined by their apolipoprotein composition. Metabolism 1992, 41:498–503.

    Article  PubMed  CAS  Google Scholar 

  67. Bard JM, Parra HJ, Douste-Blazy P, et al.: Effect of pravastatin, an HMG CoA reductase inhibitor, and cholestyramine, a bile acid sequestrant, on lipoprotein particles defined by their apolipoprotein composition. Metabolism 1990, 39:269–273.

    Article  PubMed  CAS  Google Scholar 

  68. Schweitzer M, Tessier D, Vlahos WD, et al.: A comparison of pravastatin and gemfibrozil in the treatment of dyslipoproteinemia in patients with non-insulin-dependent diabetes mellitus. Atherosclerosis 2002, 162:201–210.

    Article  PubMed  CAS  Google Scholar 

  69. Alaupovic P, Heinonen T, Shurzinske L, et al.: Effect of a new HMG-CoA reductase inhibitor, atorvastatin, on lipids, apolipoproteins and lipoprotein particles in patients with elevated serum cholesterol and triglyceride levels. Atherosclerosis 1997, 133:123–133.

    Article  PubMed  CAS  Google Scholar 

  70. Alaupovic P, Knight-Gibson C, Plotkin D, et al.: Effect of simvastatin on apoB-containing lipoproteins in patients with hypertriglyceridemia. Abstract Book, XIV International Symposium on Drugs Affecting Lipid Metabolism. New York: NY. 2001.

  71. Delplanque B, Richard JL, Jacotot B: Influence of diet on the plasma levels and distribution of apoA-I-containing lipoprotein particles. Prog Lipid Res 1991, 30:159–170.

    Article  PubMed  CAS  Google Scholar 

  72. Fumeron F, Brigant L, Parra HJ, et al.: Lowering of HDL2-cholesterol and lipoprotein A-I particle levels by increasing the ratio of polyunsaturated to saturated fatty acids. Am J Clin Nutr 1991, 53:655–659.

    PubMed  CAS  Google Scholar 

  73. Cheung MC, Lichtenstein AH, Schaefer EJ: Effects of a diet restricted in saturated fatty acids and cholesterol on the composition of apolipoprotein A-I-containing lipoprotein particles in the fasting and fed states. Am J Clin Nutr 1994, 60:911–918.

    PubMed  CAS  Google Scholar 

  74. Montoya MT, Porres A, Serrano S, et al.: Fatty acid saturation of the diet and plasma lipid concentrations, lipoprotein particle concentrations, and cholesterol efflux capacity. Am J Clin Nutr 2002, 75:484–491.

    PubMed  CAS  Google Scholar 

  75. Lee DM, Alaupovic P, Gibson C, et al.: Effect of postprandial state on lipids, apolipoproteins and lipoprotein particles in normal and hypertriglyceridemic subjects. Atherosclerosis 1994, 109:217.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Lipid and Lipoprotein Laboratory, Oklahoma Medical Research Foundation, 800 Research Parkway, Suite 340, 73104, Oklahoma City, OK, USA

    Petar Alaupovic PhD

Authors
  1. Petar Alaupovic PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alaupovic, P. The concept of apolipoprotein-defined lipoprotein families and its clinical significance. Curr Atheroscler Rep 5, 459–467 (2003). https://doi.org/10.1007/s11883-003-0036-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-003-0036-8

Keywords

Search

Navigation