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. 1991 Dec;88(6):2059–2066. doi: 10.1172/JCI115535

Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia.

C J Mann 1, F T Yen 1, A M Grant 1, B E Bihain 1
PMCID: PMC295801  PMID: 1752964

Abstract

Plasma net cholesteryl ester (CE) transfer and optimum cholesteryl ester transfer protein (CETP) activity were determined in primary hypertriglyceridemic (n = 11) and normolipidemic (n = 15) individuals. The hypertriglyceridemic group demonstrated threefold greater net CE transfer leading to enhanced accumulation of CE in VLDL. This increased net transfer was not accompanied by a change in CETP activity. In normolipidemia, but not in hypertriglyceridemia, net CE transfer correlated with VLDL triglyceride (r = 0.92, P less than 0.001). In contrast, net CE transfer in hypertriglyceridemia, but not in normolipidemia, correlated with CETP activity (r = 0.73, P less than 0.01). Correction of hypertriglyceridemia with bezafibrate reduced net CE transfer towards normal and restored the correlation with VLDL triglyceride (r = 0.90, P less than 0.005) while suppressing the correlation with CETP activity. That net CE transfer depends on VLDL concentration was confirmed by an increase of net CE transfer in normolipidemic plasma supplemented with purified VLDL. Supplementation of purified CETP to normolipidemic plasma did not stimulate net CE transfer. In contrast, net CE transfer was enhanced by addition of CETP to both plasma supplemented with VLDL and hypertriglyceridemic plasma. Thus, in normal subjects, VLDL concentration determines the rate of net CE transfer. CETP becomes rate limiting as VLDL concentration increases, i.e., in hypertriglyceridemia.

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Selected References

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  1. Agellon L. B., Walsh A., Hayek T., Moulin P., Jiang X. C., Shelanski S. A., Breslow J. L., Tall A. R. Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice. J Biol Chem. 1991 Jun 15;266(17):10796–10801. [PubMed] [Google Scholar]
  2. Albers J. J., Tollefson J. H., Chen C. H., Steinmetz A. Isolation and characterization of human plasma lipid transfer proteins. Arteriosclerosis. 1984 Jan-Feb;4(1):49–58. doi: 10.1161/01.atv.4.1.49. [DOI] [PubMed] [Google Scholar]
  3. Barter P. J., Hopkins G. J., Calvert G. D. Transfers and exchanges of esterified cholesterol between plasma lipoproteins. Biochem J. 1982 Oct 15;208(1):1–7. doi: 10.1042/bj2080001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown M. L., Inazu A., Hesler C. B., Agellon L. B., Mann C., Whitlock M. E., Marcel Y. L., Milne R. W., Koizumi J., Mabuchi H. Molecular basis of lipid transfer protein deficiency in a family with increased high-density lipoproteins. Nature. 1989 Nov 23;342(6248):448–451. doi: 10.1038/342448a0. [DOI] [PubMed] [Google Scholar]
  5. Castelli W. P., Doyle J. T., Gordon T., Hames C. G., Hjortland M. C., Hulley S. B., Kagan A., Zukel W. J. HDL cholesterol and other lipids in coronary heart disease. The cooperative lipoprotein phenotyping study. Circulation. 1977 May;55(5):767–772. doi: 10.1161/01.cir.55.5.767. [DOI] [PubMed] [Google Scholar]
  6. Castelli W. P., Garrison R. J., Wilson P. W., Abbott R. D., Kalousdian S., Kannel W. B. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA. 1986 Nov 28;256(20):2835–2838. [PubMed] [Google Scholar]
  7. Castro G. R., Fielding C. J. Effects of postprandial lipemia on plasma cholesterol metabolism. J Clin Invest. 1985 Mar;75(3):874–882. doi: 10.1172/JCI111786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deckelbaum R. J., Eisenberg S., Oschry Y., Butbul E., Sharon I., Olivecrona T. Reversible modification of human plasma low density lipoproteins toward triglyceride-rich precursors. A mechanism for losing excess cholesterol esters. J Biol Chem. 1982 Jun 10;257(11):6509–6517. [PubMed] [Google Scholar]
  9. Eisenberg S., Gavish D., Oschry Y., Fainaru M., Deckelbaum R. J. Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia. Reversal toward normal with bezafibrate treatment. J Clin Invest. 1984 Aug;74(2):470–482. doi: 10.1172/JCI111444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fielding C. J. Factors affecting the rate of catalyzed transfer of cholesteryl esters in plasma. Am Heart J. 1987 Feb;113(2 Pt 2):532–537. doi: 10.1016/0002-8703(87)90627-2. [DOI] [PubMed] [Google Scholar]
  11. Fielding P. E., Fielding C. J., Havel R. J., Kane J. P., Tun P. Cholesterol net transport, esterification, and transfer in human hyperlipidemic plasma. J Clin Invest. 1983 Mar;71(3):449–460. doi: 10.1172/JCI110789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gidez L. I., Miller G. J., Burstein M., Slagle S., Eder H. A. Separation and quantitation of subclasses of human plasma high density lipoproteins by a simple precipitation procedure. J Lipid Res. 1982 Nov;23(8):1206–1223. [PubMed] [Google Scholar]
  13. Gordon D. J., Knoke J., Probstfield J. L., Superko R., Tyroler H. A. High-density lipoprotein cholesterol and coronary heart disease in hypercholesterolemic men: the Lipid Research Clinics Coronary Primary Prevention Trial. Circulation. 1986 Dec;74(6):1217–1225. doi: 10.1161/01.cir.74.6.1217. [DOI] [PubMed] [Google Scholar]
  14. Inazu A., Brown M. L., Hesler C. B., Agellon L. B., Koizumi J., Takata K., Maruhama Y., Mabuchi H., Tall A. R. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med. 1990 Nov 1;323(18):1234–1238. doi: 10.1056/NEJM199011013231803. [DOI] [PubMed] [Google Scholar]
  15. Jonas A., Sweeny S. A., Herbert P. N. Discoidal complexes of A and C apolipoproteins with lipids and their reactions with lecithin: cholesterol acyltransferase. J Biol Chem. 1984 May 25;259(10):6369–6375. [PubMed] [Google Scholar]
  16. 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]
  17. McPherson R., Mann C. J., Tall A. R., Hogue M., Martin L., Milne R. W., Marcel Y. L. Plasma concentrations of cholesteryl ester transfer protein in hyperlipoproteinemia. Relation to cholesteryl ester transfer protein activity and other lipoprotein variables. Arterioscler Thromb. 1991 Jul-Aug;11(4):797–804. doi: 10.1161/01.atv.11.4.797. [DOI] [PubMed] [Google Scholar]
  18. Morton R. E. Free cholesterol is a potent regulator of lipid transfer protein function. J Biol Chem. 1988 Sep 5;263(25):12235–12241. [PubMed] [Google Scholar]
  19. Morton R. E., Zilversmit D. B. Inter-relationship of lipids transferred by the lipid-transfer protein isolated from human lipoprotein-deficient plasma. J Biol Chem. 1983 Oct 10;258(19):11751–11757. [PubMed] [Google Scholar]
  20. Nikkilä E. A., Taskinen M. R., Sane T. Plasma high-density lipoprotein concentration and subfraction distribution in relation to triglyceride metabolism. Am Heart J. 1987 Feb;113(2 Pt 2):543–548. doi: 10.1016/0002-8703(87)90629-6. [DOI] [PubMed] [Google Scholar]
  21. Phillips N. R., Havel R. J., Kane J. P. Levels and interrelationships of serum and lipoprotein cholesterol and triglycerides. Association with adiposity and the consumption of ethanol, tobacco, and beverages containing caffeine. Arteriosclerosis. 1981 Jan-Feb;1(1):13–24. doi: 10.1161/01.atv.1.1.13. [DOI] [PubMed] [Google Scholar]
  22. Tall A. R. Plasma lipid transfer proteins. J Lipid Res. 1986 Apr;27(4):361–367. [PubMed] [Google Scholar]
  23. Tall A. R., Sammett D., Vita G. M., Deckelbaum R., Olivecrona T. Lipoprotein lipase enhances the cholesteryl ester transfer protein-mediated transfer of cholesteryl esters from high density lipoproteins to very low density lipoproteins. J Biol Chem. 1984 Aug 10;259(15):9587–9594. [PubMed] [Google Scholar]
  24. Tall A., Granot E., Brocia R., Tabas I., Hesler C., Williams K., Denke M. Accelerated transfer of cholesteryl esters in dyslipidemic plasma. Role of cholesteryl ester transfer protein. J Clin Invest. 1987 Apr;79(4):1217–1225. doi: 10.1172/JCI112940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tall A., Sammett D., Granot E. Mechanisms of enhanced cholesteryl ester transfer from high density lipoproteins to apolipoprotein B-containing lipoproteins during alimentary lipemia. J Clin Invest. 1986 Apr;77(4):1163–1172. doi: 10.1172/JCI112417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vakakis N., Redgrave T. G., Small D. M., Castelli W. P. Cholesterol content of red blood cells and low-density lipoproteins in hypertriglyceridemia. Biochim Biophys Acta. 1983 May 16;751(3):280–285. doi: 10.1016/0005-2760(83)90285-0. [DOI] [PubMed] [Google Scholar]
  27. Yen F. T., Deckelbaum R. J., Mann C. J., Marcel Y. L., Milne R. W., Tall A. R. Inhibition of cholesteryl ester transfer protein activity by monoclonal antibody. Effects on cholesteryl ester formation and neutral lipid mass transfer in human plasma. J Clin Invest. 1989 Jun;83(6):2018–2024. doi: 10.1172/JCI114112. [DOI] [PMC free article] [PubMed] [Google Scholar]

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