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. 1983 Nov;80(21):6662–6666. doi: 10.1073/pnas.80.21.6662

Composition and distribution of low density lipoprotein fractions in hyperapobetalipoproteinemia, normolipidemia, and familial hypercholesterolemia.

B Teng, G R Thompson, A D Sniderman, T M Forte, R M Krauss, P O Kwiterovich Jr
PMCID: PMC391230  PMID: 6579550

Abstract

Hyperapobetalipoproteinemia is defined as the combination of a normal low density lipoprotein (LDL) cholesterol in the face of an increased LDL apolipoprotein B (apoB) protein. To examine the physical basis for the apparent disproportion between LDL cholesterol and apoB characteristic of this syndrome, we used density gradient ultracentrifugation to isolate LDL fractions from 10 normal subjects, from 20 patients with hyperapobetalipoproteinemia (10 normotriglyceridemic and 10 hypertriglyceridemic), and from 7 patients with familial hypercholesterolemia. In familial hypercholesterolemia, more LDL was in fraction 1--"light" LDL--and this LDL was relatively enriched in cholesterol and poor in protein. By contrast, it was fraction 2--"heavy" LDL--that differed in hyperapobetalipoproteinemia, being denser, depleted of cholesterol (particularly cholesteryl ester), and relatively enriched in apoB. These findings were more pronounced in the hypertriglyceridemic patients than in the normotriglyceridemic patients with hyperapobetalipoproteinemia. Thus this study confirms that considerable heterogeneity exists between LDL subfractions within individuals but, in addition, indicates there are also marked--and apparently characteristic--differences in LDL composition amongst normal subjects and patients with hyperapobetalipoproteinemia or familial hypercholesterolemia.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams G. H., Schumaker V. N. Equilibrium banding of low-density lipoproteins. 3. Studies on normal individuals and the effects of diet and heparin-induced lipase. Biochim Biophys Acta. 1970 Sep 8;210(3):462–472. doi: 10.1016/0005-2760(70)90043-3. [DOI] [PubMed] [Google Scholar]
  2. Avogaro P., Bon G. B., Cazzolato G., Quinci G. B. Are apolipoproteins better discriminators than lipids for atherosclerosis? Lancet. 1979 Apr 28;1(8122):901–903. doi: 10.1016/s0140-6736(79)91375-8. [DOI] [PubMed] [Google Scholar]
  3. Avogaro P., Bon G. B., Cazzolato G., Quinci G. B., Sanson A., Sparla M., Zagatti G. C., Caturelli G. Variations in apolipoproteins B and A1 during the course of myocardial infarction. Eur J Clin Invest. 1978 Jun;8(3):121–129. doi: 10.1111/j.1365-2362.1978.tb00824.x. [DOI] [PubMed] [Google Scholar]
  4. De Backer G., Rosseneu M., Deslypere J. P. Discriminative value of lipids and apoproteins in coronary heart disease. Atherosclerosis. 1982 Apr;42(2-3):197–203. doi: 10.1016/0021-9150(82)90150-2. [DOI] [PubMed] [Google Scholar]
  5. Durrington P. N., Bolton C. H., Hartog M. Serum and lipoprotein apolipoprotein B levels in normal subjects and patients with hyperlipoproteinaemia. Clin Chim Acta. 1978 Jan 2;82(1-2):151–160. doi: 10.1016/0009-8981(78)90038-4. [DOI] [PubMed] [Google Scholar]
  6. Fisher W. R. Heterogeneity of plasma low density lipoproteins manifestations of the physiologic phenomenon in man. Metabolism. 1983 Mar;32(3):283–291. doi: 10.1016/0026-0495(83)90194-4. [DOI] [PubMed] [Google Scholar]
  7. Forte T., Norum K. R., Glomset J. A., Nichols A. V. Plasma lipoproteins in familial lecithin: cholesterol acyltransferase deficiency: structure of low and high density lipoproteins as revealed by elctron microscopy. J Clin Invest. 1971 May;50(5):1141–1148. doi: 10.1172/JCI106586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fruchart J. C., Parra H., Cachera C., Clavey V., Bertrand M. Lipoproteins, apolipoproteins and coronary artery disease. Ric Clin Lab. 1982 Jan-Mar;12(1):101–106. doi: 10.1007/BF02909314. [DOI] [PubMed] [Google Scholar]
  9. Glomset J. A., Applegate K., Forte T., King W. C., Mitchell C. D., Norum K. R., Gjone E. Abnormalities in lipoproteins of d < 1.006 g/ml in familial lecithin:cholesterol acyltransferase deficiency. J Lipid Res. 1980 Nov;21(8):1116–1127. [PubMed] [Google Scholar]
  10. Goldstein J. L., Hazzard W. R., Schrott H. G., Bierman E. L., Motulsky A. G. Hyperlipidemia in coronary heart disease. I. Lipid levels in 500 survivors of myocardial infarction. J Clin Invest. 1973 Jul;52(7):1533–1543. doi: 10.1172/JCI107331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gordon T., Castelli W. P., Hjortland M. C., Kannel W. B., Dawber T. R. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977 May;62(5):707–714. doi: 10.1016/0002-9343(77)90874-9. [DOI] [PubMed] [Google Scholar]
  12. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jadhav A. V., Thompson G. R. Reversible abnormalities of low density lipoprotein composition in familial hypercholesterolaemia. Eur J Clin Invest. 1979 Feb;9(1):63–67. doi: 10.1111/j.1365-2362.1979.tb01668.x. [DOI] [PubMed] [Google Scholar]
  14. KANNEL W. B., DAWBER T. R., KAGAN A., REVOTSKIE N., STOKES J., 3rd Factors of risk in the development of coronary heart disease--six year follow-up experience. The Framingham Study. Ann Intern Med. 1961 Jul;55:33–50. doi: 10.7326/0003-4819-55-1-33. [DOI] [PubMed] [Google Scholar]
  15. Kannel W. B., Castelli W. P., Gordon T., McNamara P. M. Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med. 1971 Jan;74(1):1–12. doi: 10.7326/0003-4819-74-1-1. [DOI] [PubMed] [Google Scholar]
  16. Katz S. S., Shipley G. G., Small D. M. Physical chemistry of the lipids of human atherosclerotic lesions. Demonstration of a lesion intermediate between fatty streaks and advanced plaques. J Clin Invest. 1976 Jul;58(1):200–211. doi: 10.1172/JCI108450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Krauss R. M., Burke D. J. Identification of multiple subclasses of plasma low density lipoproteins in normal humans. J Lipid Res. 1982 Jan;23(1):97–104. [PubMed] [Google Scholar]
  18. Krauss R. M., Lindgren F. T., Ray R. M. Interrelationships among subgroups of serum lipoproteins in normal human subjects. Clin Chim Acta. 1980 Jul 1;104(3):275–290. doi: 10.1016/0009-8981(80)90385-x. [DOI] [PubMed] [Google Scholar]
  19. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  20. Lee D. M., Alaupovic P. Studies of the composition and structure of plasma lipoproteins. Isolation, composition, and immunochemical characterization of low density lipoprotein subfractions of human plasma. Biochemistry. 1970 May 26;9(11):2244–2252. doi: 10.1021/bi00813a004. [DOI] [PubMed] [Google Scholar]
  21. Lee D. M., Downs D. A quick and large-scale density gradient subfractionation method for low density lipoproteins. J Lipid Res. 1982 Jan;23(1):14–27. [PubMed] [Google Scholar]
  22. Lees R. S. Immunoassay of plasma low-density lipoproteins. Science. 1970 Jul 31;169(3944):493–495. doi: 10.1126/science.169.3944.493. [DOI] [PubMed] [Google Scholar]
  23. Mills G. L., Taylaur C. E., Chapman M. J. Low-density lipoproteins in patients homozygous for familial hyperbetalipoproteinaemia. Clin Sci Mol Med. 1976 Sep;51(3):221–231. doi: 10.1042/cs0510221. [DOI] [PubMed] [Google Scholar]
  24. Patsch W., Ostlund R., Kuisk I., Levy R., Schonfeld G. Characterization of lipoprotein in a kindred with familial hypercholesterolemia. J Lipid Res. 1982 Nov;23(8):1196–1205. [PubMed] [Google Scholar]
  25. Riesen W. F., Mordasini R., Salzmann C., Theler A., Gurtner H. P. Apoproteins and lipids as discriminators of severity of coronary heart disease. Atherosclerosis. 1980 Sep;37(1):157–162. doi: 10.1016/0021-9150(80)90104-5. [DOI] [PubMed] [Google Scholar]
  26. Shen M. M., Krauss R. M., Lindgren F. T., Forte T. M. Heterogeneity of serum low density lipoproteins in normal human subjects. J Lipid Res. 1981 Feb;22(2):236–244. [PubMed] [Google Scholar]
  27. Slack J., Mills G. L. Anomalous low density lipoproteins in familial hyperbetalipoproteinaemia. Clin Chim Acta. 1970 Jul;29(1):15–25. doi: 10.1016/0009-8981(70)90215-9. [DOI] [PubMed] [Google Scholar]
  28. Sniderman A. D., Teng B. Predictable changes in low density lipoprotein composition after acute myocardial infarction. Atherosclerosis. 1977 Jul;27(3):361–368. doi: 10.1016/0021-9150(77)90046-6. [DOI] [PubMed] [Google Scholar]
  29. Sniderman A. D., Wolfson C., Teng B., Franklin F. A., Bachorik P. S., Kwiterovich P. O., Jr Association of hyperapobetalipoproteinemia with endogenous hypertriglyceridemia and atherosclerosis. Ann Intern Med. 1982 Dec;97(6):833–839. doi: 10.7326/0003-4819-97-6-833. [DOI] [PubMed] [Google Scholar]
  30. Sniderman A., Shapiro S., Marpole D., Skinner B., Teng B., Kwiterovich P. O., Jr Association of coronary atherosclerosis with hyperapobetalipoproteinemia [increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins]. Proc Natl Acad Sci U S A. 1980 Jan;77(1):604–608. doi: 10.1073/pnas.77.1.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sniderman A., Teng B., Jerry M. Determination of B protein of low density lipoprotein directly in plasma. J Lipid Res. 1975 Nov;16(6):465–467. [PubMed] [Google Scholar]
  32. Whayne T. F., Alaupovic P., Curry M. D., Lee E. T., Anderson P. S., Schechter E. Plasma apolipoprotein B and VLDL-, LDL-, and HDL-cholesterol as risk factors in the development of coronary artery disease in male patients examined by angiography. Atherosclerosis. 1981 Jun;39(3):411–424. doi: 10.1016/0021-9150(81)90026-5. [DOI] [PubMed] [Google Scholar]
  33. Wilson D. E., Lees R. S. Metabolic relationships among the plasma lipoproteins. Reciprocal changes in the concentrations of very low and low density lipoproteins in man. J Clin Invest. 1972 May;51(5):1051–1057. doi: 10.1172/JCI106896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Witztum J. L., Schonfeld G., Weidman S. W., Giese W. E., Dillingham M. A. Bile sequestrant therapy alters the compositions of low-density and high-density lipoproteins. Metabolism. 1979 Mar;28(3):221–229. doi: 10.1016/0026-0495(79)90067-2. [DOI] [PubMed] [Google Scholar]

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