European Journal of Epidemiology

, Volume 8, Supplement 1, pp 92–98

IDL, VLDL, chylomicrons and atherosclerosis

  • B. G. Nordestgaard
  • A. Tybjærg-Hansen
Article

Abstract

In humans with the lipoprotein lipase deficiency disorder large amounts of chylomicrons and large very low-density lipoprotein (VLDL) accumulate in plasma. In spite of this, atherosclerosis does not seem to develop at an accelerated rate, suggesting that these lipoproteins do not promote atherogenesis. In humans with dysbetalipoproteinemia remnant lipoproteins (intermediate density lipoprotein (IDL) plus B-VLDL) accumulate in plasma and these particles may therefore be the factor causing accelerated atherosclerosis in this disorder.

Epidemiological studies in humans suggest that IDL or remnant lipoproteins are predictors of the severity or progression of atherosclerosis. Similar studies in the St. Thomas' Hospital rabbit strain, an animal model with genetically elevated plasma levels of VLDL, IDL and low-density lipoprotein (LDL), showed that IDL or remnant lipoproteins were better predictors of the extent of atherosclerosis than were LDL or VLDL.

Studies of lipoprotein/arterial wall interactions have demonstrated that the larger the lipoprotein particle, the lower the influx into intima. Very large VLDL and chylomicrons do not seem to enter intima. Although high-density lipoprotein (HDL) enters intima faster than other lipoproteins, the small HDL particles seem to penetrate the entire arterial wall and leave via lymphatics and vasa vasorum in the outer media and adventitia. In contrast, LDL, and possibly also IDL and smaller VLDL, may only leave the intima via the lumen of the artery.

In conclusion, a substantial body of evidence suggests that remnant lipoproteins (IDL and smaller VLDL) share with LDL the potential for promoting atherosclerosis, whereas very large VLDL and chylomicrons do not seem to have this effect.

Key words

Lipoprotein lipase deficiency Familial combined hyperlipidemia Dysbetalipoproteinemia The St. Thomas' Hospital rabbit strain Atherosclerosis Lipoprotein permeability 

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References

  1. 1.
    AustinM.A. (1989): Plasma triglyceride as a risk factor for coronary heart disease. The epidemiologic evidence and beyond - Am. J. Epidemiol.129: 249–259.Google Scholar
  2. 2.
    BrecherP.,ChobanianA.Y.,SmallD.M., et al. (1983): Relationship of an abnormal plasma lipoprotein to protection from atherosclerosis in the cholesterol-fed diabetic rabbit - J. Clin. Invest.72: 1553–1562.Google Scholar
  3. 3.
    BrownM.S.,GoldsteinJ.L. andFredricksonD.S. (1983): Familial type 3 hyperlipoproteinemia (Dysbetalipoproteinemia). In:StanburyJ.B.,WyngaardenJ.B.,FredricksonD.S.,GoldsteinJ.L. andBrownM.S. eds. The metabolic basis of inherited disease. 5th. ed. New York, N.Y.: McGraw-Hill, pp. 655–671.Google Scholar
  4. 4.
    Duff.G.L. andMcMillanG.C. (1949): The effect of alloxan diabetes on experimental cholesterol atherosclerosis in the rabbit. I. The inhibition of experimental cholesterol atherosclerosis in alloxan diabetes. II. The effect of alloxan diabetes on the retrogression of experimental cholesterol atherosclerosis - J. Exp. Med.89: 611–630.Google Scholar
  5. 5.
    GrundyS.M.,ChaitA. andBrunzellJ.D. (1987): Familial combined hyperlipidemia workshop -Arteriosclerosis7: 203–207.Google Scholar
  6. 6.
    GrundyS.M. andVegaG.L. (1988): Hypertriglyceridemia: causes and relation to coronary heart disease - Semin. Thromb. Hemost.14: 249–164.Google Scholar
  7. 7.
    KraussR.M.,LindgrenF.T.,WilliamsP.T., et al. (1987): Intermediate-density lipoproteins and progression of coronary artery disease in hypercholesterolaemic men - LancetII: 62–66.Google Scholar
  8. 8.
    LaVilleA.,TurnerP.R.,PittilaM., et al. (1987): Hereditary hyperlipidemia in the rabbit due to overproduction of lipoproteins. I. Biochemical studies - Arteriosclerosis7: 105–112.Google Scholar
  9. 9.
    McGillH.C.Jr. andHolmanR.L. (1949): The influence of alloxan diabetes on cholesterol atheromatosis in the rabbit - Proc. Soc. Exp. Biol. Med.72: 72–75.Google Scholar
  10. 10.
    MillerN.E.,HammettF.,SaltissiS., et al. (1981): Relation of angiographically defined coronary artery disease to plasma lipoprotein subfractions and apolipoproteins - Br. Med. J.282: 1741–1744.Google Scholar
  11. 11.
    MinnichA. andZilversmitD.B. (1989): Impaired triacylglycerol catabolism in hypertriglyceridemia of the diabetic, cholesterol-fed rabbit: a possible mechanism for protection from atherosclerosis -Biochem. Biophys. Acta1002: 324–332.Google Scholar
  12. 12.
    NicollA.,DuffieldR. andLewisB. (1981): Flux of plasma lipoproteins into human arterial intima. Comparison between grossly normal and atheromatous intima - Atherosclerosis39: 229–242.Google Scholar
  13. 13.
    NiehausC.E.,NicollA.,WoottonR., et al. (1977): Influence of lipid concentrations and age on transfer of plasma lipoprotein into human arterial intima -LancetII: 469–471.Google Scholar
  14. 14.
    NikkiläE.A. (1983): Familial lipoprotein lipase deficiency and related disorders of chylomicron metabolism. In: Stanbury J.B., Wyngaarden J.B., Fredrickson D.S., Goldstein J.L., and Brown M.S., eds. The metabolic basis of inherited disease. 5th ed. -New York, N.Y.: McGraw-Hill pp. 622–642.Google Scholar
  15. 15.
    NordestgaardB.G.,HjelmsE.,StenderS. andKjeldsenK. (1990): Different efflux pathways for high and low density lipoproteins from porcine aortic intima -Arteriosclerosis10: 477–485.Google Scholar
  16. 16.
    NordestgaardB.G. andLewisB. (1991): Intermediate-density lipoprotein levels are strong predictors of the extent of aortic atherosclerosis in the St. Thomas's Hospital rabbit strain - Atherosclerosis87: 39–46.Google Scholar
  17. 17.
    NordestgaardB.G.,StenderS. andKjeldsenK. (1988): Reduced atherogenesis in cholesterol-fed diabetic rabbits. Giant lipoproteins do not enter the arterial wall - Arteriosclerosis8: 421–428.Google Scholar
  18. 18.
    NordestgaardB.G.,Tybjærg-HansenA. andLewisB. (1992): Influxin vivo of low-density, intermediate-density, and very low-density lipoproteins into aortic intima of genetically hyperlipidemic rabbits: roles of plasma concentration, extent of aortic lesion, and lipoprotein particle size as determinants -Arteriosclerosis and Thrombosis12: 6–18.Google Scholar
  19. 19.
    NordestgaardB.G. andZilversmitD.B. (1988): Large lipoproteins are excluded from the arterial wall in diabetic cholesterol-fed rabbits - J. Lipid. Res.29: 1491–1500.Google Scholar
  20. 20.
    NordestgaardB.G. andZilversmitD.B. (1989): Comparison of arterial intimal clearances of LDL from diabetic and nondiabetic cholesterol-fed rabbits. Differences in intimal clearance explained by size differences - Arteriosclerosis9: 176–183.Google Scholar
  21. 21.
    ReadornM.F.,FidgeN.H. andNestelP.J. (1978): Catabolism of very low-density lipoprotein B apoprotein in man - J. Clin. Invest.61: 850–860.Google Scholar
  22. 22.
    ReadonM.E.,NestelP.J.,CraigI.H. andHarperR.W. (1985): Lipoprotein predictors of the severity of coronary artery disease in men and women -Circulation71: 881–888.Google Scholar
  23. 23.
    SeddonA.M.,WoofN.,LaVilleA., et al. (1987): Hereditary hyperlipidemia and atherosclerosis in the rabbit due to overproduction of lipoproteins. II. Preliminary report of arterial pathology -Arteriosclerosis7: 113–124.Google Scholar
  24. 24.
    ShaikhM.,WoottonR.,NordestgaardB.G., et al. (1991): Quantitative studies of transfer in vivo of lowdensity, Sf 12–60 and Sf 60–400 lipoproteins between plasma and arterial intima in humans -Arteriosclerosis and Thrombosis11: 569–577.Google Scholar
  25. 25.
    SteinerG.,SchwartzL.,ShumakS. andPoapstM. (1987): The association of increased levels of intermediate-density lipoproteins with smoking and with coronary artery disease - Circulation75: 124–130.Google Scholar
  26. 26.
    StenderS. andHjelmsE. (1987):In vivo transfer of cholesterol from plasma into human aortic tissue -Scand. J. Clin. Lab. Invest.47 suppl.186: 21–29.Google Scholar
  27. 27.
    StenderS. andHjelmsE. (1988):In vivo transfer of cholesteryl ester from high- and low-density plasma lipoproteins into human aortic tissue -Arteriosclerosis8: 252–262.Google Scholar
  28. 28.
    StenderS. andZilversmitD.B. (1981): Transfer of plasma lipoprotein components and of plasma proteins into aortas of cholesterol-fed rabbits. Molecular size as a determinant of plasma lipoprotein influx - Arteriosclerosis1: 38–49.Google Scholar
  29. 29.
    SukaK.,CedresC.,McDonaldB., et al. (1984): C-II anapolipoproteinemia and severe hypertriglyceridemia. Report of a rare case with absence of C-II apolipoprotein isoforms and review of the literature. - Am. J. Med.77: 457–462.Google Scholar
  30. 30.
    TatamiR.,MabuchiH.,UedaK., et al. (1981): Intermediate-density lipoprotein and cholesterol-rich very low-density lipoprotein in angiographically determined coronary artery disease - Circulation64: 1174–1184.Google Scholar
  31. 31.
    WoottonR.,BaskervilleP.,TurnerP., et al. (1987): A method for quantifying lipoprotein flux rates between plasma and arterial intimain vivo - Clin. Phys. Physiol. Meas.8: 65–74.Google Scholar

Copyright information

© Gustav Fischer 1992

Authors and Affiliations

  • B. G. Nordestgaard
    • 1
  • A. Tybjærg-Hansen
    • 2
    • 3
  1. 1.Department of Medicine B - Division of Cardiology and Department of Clinical Chemistry RigshospitaletUniversity of CopenhagenCopenhagen ØDenmark
  2. 2.The Charing Cross Sunley Research CentreLondon United Kingdom
  3. 3.Hagedorn Research LaboratoryGentofteDenmark

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