Apo-Lipoprotein Localization in Human Atherosclerotic Arteries

  • H. F. Hoff
  • R. L. Jackson
  • A. M. GottoJr.
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 67)


A study documenting the localization in human arteries of apoproteins from human plasma high density (HDL), low density (LDL), and very low density (VLDL) lipoproteins was undertaken in light of their possible roles in the pathogenesis and regression of the atherosclerotic process in man. Apo A-I from HDL, apo B from LDL, apo C-III from VLDL were all localized by immunohistochemical techniques to generally the same areas of atherosclerotic lesions. These consisted of certain bands of collagen and elastic fibers in fatty streaks and fibrous plaques, and extracellular pools of neutral lipid in fibrous plaques. Apoproteins were also occasionally present in areas of diffuse intimal thickening in coronary arteries. Extensiveness and frequency of appearance of apo B in atherosclerotic lesions was greatest in type II hyperlipoproteinemics, thus correlating with the plasma apo B levels. Employing an immuno-peroxidase procedure, apo B was localized ultra-structurally in atherosclerotic lesions to the outer surface of spheres ranging in diameter between 250 and 700 A. These spheres, localized predominantly in lipid cores and between collagen bands, were also seen in negatively-stained preparations of arterial extracts which also reacted positively against anti-apo B, suggesting that the spheres may represent native LDL and VLDL. The superimposed localization of apo A-I, apo B, and apo C-III in atherosclerotic lesions suggests that a specific interaction exists between certain lesion components and these apoproteins.


Neutral Lipid Atherosclerotic Lesion High Density Lipoprotein Lipid Core Collagen Band 
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  1. 1.
    Dawber, T.R., F.E. More, and J.V. Mann. 1957. Coronary heart disease in the Framingham Study. Am. J. Public Health 47 (Suppl. 4):4–24.Google Scholar
  2. 2.
    Kannel, W.B., T.R. Dawber, and G.D. Friedman. 1964. Risk factors in coronary heart disease: An evaluation of several serum lipids as predictors of coronary heart disease. The Framingham Study. Am. Intern. Med. 61:888–899.CrossRefGoogle Scholar
  3. 3.
    Kannel, W.B., T. Gordon, and T.R. Dawber. 1974. Role of lipids in the development of brain infarction. The Framingham Study. Stroke 5:679–685.CrossRefGoogle Scholar
  4. 4.
    Goldstein, J.L., W.R. Hazzard, H.G. Schrodt, E.L. Bierman, and A.F. Motulsky. 1973. Hyperlipidemia in coronary heart disease: I. Lipid levels in 500 survivors of myocardial infarction. J. Clin. Invest. 52:1533–1577.PubMedCrossRefGoogle Scholar
  5. 5.
    Smith, E.B. 1974. Relationship between plasma and tissue lipids in human atherosclerosis. Adv. Lipid Res. 12:1–49.PubMedGoogle Scholar
  6. 6.
    Adams, C.W.M. 1971. Lipids, lipoproteins and atherosclerotic lesions. Proc. Roy. Soc. Med. 64:902–905.PubMedGoogle Scholar
  7. 7.
    Goldstein, J.L., and M.D. Brown. 1975. Lipoprotein receptors, cholesterol metabolism, and atherosclerosis. Arch. Pathol. 99:181–184.PubMedGoogle Scholar
  8. 8.
    Fischer-Dzoga, K., R.M. Jones, D. Vesselinovitch, and R.W. Wissler. 1974. Increased mitotic activity in primary cultures of aortic medial smooth muscle cells after exposure to hyperlipemic serum. In: Atherosclerosis, III, Proc. Third Inter. Symposium on Atherosclerosis Ed. by G. Schettler and A. Weizel, Springer-Verlag, New York, pp. 193–195.CrossRefGoogle Scholar
  9. 9.
    Ross, R. and J.A. Glomset. 1973. Atherosclerosis and the arterial smooth muscle cell. Science 180:1332–1339.PubMedCrossRefGoogle Scholar
  10. 10.
    Stein, Y., M.C. Glangeaud, M. Fainaru, and O. Stein. 1975. The removal of cholesterol from aortic smooth muscle cells in culture and Landschutz ascites cells by fractions of human high density apolipoproteins. Biochim. Biophys. Acta. 380:106–118.PubMedCrossRefGoogle Scholar
  11. 11.
    Jackson, R.L., O. Stein, A.M. Gotto, and Y. Stein. 1975. A comparative study on the removal of cellular lipids from Landschutz ascites cells by human plasma apolipoproteins. J. Biol. Chem. 250:7204–7209.PubMedGoogle Scholar
  12. 12.
    Pearlstein, E., P. Eggena, and F. Aladjem. 1971. Human serum high density lipoproteins and chylomicrons. Immunochemistry 8:865–87.PubMedCrossRefGoogle Scholar
  13. 13.
    Hoff, H.F., R.L. Jackson, J.T. Mao, and A.M. Gotto. 1974. Localization of low density lipoproteins in arterial lesions from normolipemics employing a purified fluorescent-labeled antibody. Biochim. Biophys. Acta. 351:407–415.PubMedCrossRefGoogle Scholar
  14. 14.
    Hoff, H.F., J.T. Lie, J.L. Titus, R.L. Jackson, R. Bayardo, M.E. DeBakey, and A.M. Gotto. 1975. Localization of apo-low density lipoproteins (apo LDL) in atherosclerotic lesions of human normo-and hyperlipemics. Arch. Pathol. 99:253–258.PubMedGoogle Scholar
  15. 15.
    Modesto, R.R., and A.J. Pesce. 1973. Use of tolylene diisocyanate for the preparation of a peroxidase-labelled antibody conjugate: Quantitation of the amount of diisocyanate bound. Biochim. Biophys. Acta. 295:283–295.PubMedCrossRefGoogle Scholar
  16. 16.
    Frederickson, D.S., and R.I. Levy. 1972. Familial hyperlipoproteinemia. In: Metabolic Basis of Inherited Diseases. Ed. by J.B. Standburg, J.B. Wyngaarden, and D.S. Frederickson, McGraw-Hill Book Company, New York, p. 545.Google Scholar
  17. 17.
    Hoff, H.F., and J.W. Gaubatz. 1976. Ultrastructural localization of plasma lipoproteins in human intracranial arteries. Virchows Archiv (in press).Google Scholar
  18. 18.
    Hoff, H.F., C.L. Heideman, R.L. Jackson, R.J. Bayardo, H.S. Kim, and A.M. Gotto. 1975. Localization patterns of plasma apolipoproteins in human atherosclerotic lesions. Circ Res. 37:72–79.PubMedCrossRefGoogle Scholar
  19. 19.
    Kao, V.C., and R.W. Wissler. 1965. A study of the immunohistochemical localization of serum lipoproteins and other plasma proteins in human atherosclerotic lesions. Exp. Mol. Path. 4:465–479.CrossRefGoogle Scholar
  20. 20.
    Walton, K.W., and N. Williamson. 1968. Histological and immunofluorescent studies on the human atheromatous plaque. J. Atheroscler. Res. 8:599–624.PubMedCrossRefGoogle Scholar
  21. 21.
    Walton, K.W. 1974. Identification of lipoproteins involved in human atherosclerosis. In: Atherosclerosis III, Proc. Third Inter. Symposium on Atherosclerosis. Ed. by G. Schettler and A. Weizel, Springer-Verlag, Berlin, Heidelberg, New York, pp. 93–95.CrossRefGoogle Scholar
  22. 22.
    Zilversmit, D. 1973. A proposal linking atherogenesis to the interaction of endothelial lipoprotein lipase with triglyceriderich lipoproteins. Circ. Res. 33:633–638.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1976

Authors and Affiliations

  • H. F. Hoff
    • 1
  • R. L. Jackson
    • 1
  • A. M. GottoJr.
    • 1
  1. 1.Departments of Neurology and MedicineBaylor College of Medicine and The Methodist HospitalHoustonUSA

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