Advertisement

Mechanism of Inhibition of Cholesterol Uptake by the Arterial Wall

  • R. J. Bing
  • J. S. M. Sarma
  • R. Fischer
  • S. Ikeda
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 67)

Abstract

Our early studies on in vitro perfused aortas and coronary arteries have dealt with lipid synthesis and cholesterol (cholest-5-en-3β-ol) uptake by the arterial wall. In the course of these studies, we noticed that the addition of 7-ketocholesterol (3β-hydroxycholest-5-en-7one) to the perfusion fluid resulted in a significant inhibition of cholesterol uptake by the arterial wall of different species, without interfering with lipid synthesis. Because of this finding, this report will be primarily concerned with this inhibition and its mechanisms. However earlier studies on lipid synthesis and cholesterol uptake by isolated perfused arteries will also be discussed since the technique and the results have a bearing on inhibitory effects of 7-ketocholesterol.

Keywords

Bile Salt Arterial Wall Lipid Synthesis Familial Hypercholesterolemia Cholesterol Uptake 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Morita, T. and R.J, Bing. 1972. Lipid metabolism in perfused human coronary arteries. Proc. Soc. Exp. Biol. Med. 140: 617–622.PubMedGoogle Scholar
  2. 2.
    Hashimoto, H., H. Tillmanns, J.S.M. Sarma, J. Mao, E. Holden, and R.J. Bing. 1974. Lipid metabolism in perfused human non-atherosclerotic coronary arteries and saphenous veins. Atherosclerosis 19:35–45.PubMedCrossRefGoogle Scholar
  3. 3.
    Sarma, J.S.M., H. Tillmanns, S. Ikeda, A. Grenier, E. Colby, and R.J. Bing. 1975. Lipid metabolism in perfused human and dog coronary arteries. Amer. J. Cardiol. 35:579–587.PubMedCrossRefGoogle Scholar
  4. 4.
    Bing, R.J. and J.S.M. Sarma. 1975. In vitro inhibition of cholesterol uptake in human and animal arteries by 7-ketocholesterol. Biochem. Biophys. Res. Coram. 62:711–716.CrossRefGoogle Scholar
  5. 5.
    Sarma, J.S.M., R. Fischer, S. Ikeda, and R.J. Bing. In vivo inhibition of cholesterol uptake in rabbit aortas by 7-ketocholesterol. In press.Google Scholar
  6. 6.
    Carrel, A., and C.A. Lindbergh. 1938. The Culture of Organs. Harper and Row, New York.Google Scholar
  7. 7.
    Freeman, C.P. and D. West. 1966. Complete separation of lipid classes on a single thin-layer plate. J. Lipid Res. 7:324–328.PubMedGoogle Scholar
  8. 8.
    Van Lier, J.E. and L.L. Smith. 1968. Sterol metabolism II. Gas Chromatographic recognition of cholesterol metabolites and artifacts. Anal.Biochem. 24:419–430.PubMedCrossRefGoogle Scholar
  9. 9.
    Zak, B., R.C. Dickenman, E.G. White, H. Burnett, and P.J. Cherney. 1954. Rapid estimation of free and total cholesterol. Amer. J. Clin. Path. 24:1307–1315.Google Scholar
  10. 10.
    Sarma, J.S.M., R. Fischer, S. Ikeda, and R.J. Bing. The fate of labelled 7-ketocholesterol in the body (in preparation).Google Scholar
  11. 11.
    Zilversmit, D.B. 1975. Mechanisms of cholesterol accumulation in the arterial wall. Amer. J. Cardiol. 35:559–566.PubMedCrossRefGoogle Scholar
  12. 12.
    Nilsson, A., D.B. Zilversmit. 1972. Fate of intravenously administered particulate and lipoprotein cholesterol in the rat. J. Lipid Res. 13:32–38.PubMedGoogle Scholar
  13. 13.
    Zilversmit, D.B. 1968. Cholesterol flux in the atherosclerotic plaque. Ann. N.Y. Acad. Sci. 149:710–724.PubMedCrossRefGoogle Scholar
  14. 14.
    Newman, H.A.I. and D.B. Zilversmit. 1962. Quantitative aspects of cholesterol flux in rabbit. J. Biol. Chem. 237:2078–2081.PubMedGoogle Scholar
  15. 15.
    Chobanian, A.V., W. Hollander. 1962. Body cholesterol metabolism in man. I. The equilibration of serum and tissue cholesterol. J. Clin. Invest. 41:1732–1737.PubMedCrossRefGoogle Scholar
  16. 16.
    Gould, R.G., R.W. Wissler, R.J. Jones. 1963. The dynamics of lipid deposition in arteries. In: Evolution of the atherosclerotic Plaque. Edited by R.J. Jones. University of Chicago Press, Chicago, pp. 205–214.Google Scholar
  17. 17.
    Dayton, S., S. Hashimoto. 1970. Recent advances in molecular pathology: cholesterol flux and metabolism in arterial tissue and in atheromata. Exp. Mol. Pathol. 13:253–268.PubMedCrossRefGoogle Scholar
  18. 18.
    Jensen, J. 1967. The kinetics of the in vitro cholesterol uptake at the endothelial cell surface of the rabbit aorta. Biochem. Biophys. Acta 135:544–556.PubMedCrossRefGoogle Scholar
  19. 19.
    Bay, A.J., M.L. Wahlqvist, D.J. Campbell. 1970. Differential uptake of cholesterol and of different cholesterol esters by atherosclerotic intima in vivo and in vitro. Atherosclerosis 11:301–320.CrossRefGoogle Scholar
  20. 20.
    Newman, H.A.I., D.B. Zilversmit. 1966. Uptake and release of cholesterol by rabbit atheromatous lesions. Circ. Res. 18:293–302.PubMedCrossRefGoogle Scholar
  21. 21.
    Dayton, S., S. Hashimoto. 1966. Movement of labeled cholesterol between plasma lipoprotein and normal arterial wall across the intimai surface. Circ. Res. 19:1041–1049.PubMedCrossRefGoogle Scholar
  22. 22.
    Zilversmit, D.B., H.A.I. Newman. 1966. Does a metabolic barrier to circulating cholesterol protect the arterial wall? Circulation 33: 7.PubMedCrossRefGoogle Scholar
  23. 23.
    Somer, J.B., C.J. Schwartz. 1971. Focal 3H-cholesterol uptake in the pig aorta. Atherosclerosis 13:293–304.PubMedCrossRefGoogle Scholar
  24. 24.
    Bondjers, G., S. Björkerud. 1973. Cholesterol accumulation and content in regions with defined endothelial integrity in the normal rabbit aorta. Atherosclerosis 17:71–83.PubMedCrossRefGoogle Scholar
  25. 25.
    Mitton, J.R., N.A. Scholan and G.S. Boyd. 1971. The oxidation of cholesterol in rat liver subcellular particles. The cholesterol-7α-hydroxylase enzyme system. Eur. J. Biochem. 20:569–579.CrossRefGoogle Scholar
  26. 26.
    Van Lier, J.E. and L.L. Smith. 1967. Sterol metabolism. I. 26-hydroxycholesterol in the human aorta. Biochem. 6:3269–3278.CrossRefGoogle Scholar
  27. 27.
    Hardegger, E.L. Ruzicka, and E. Tagmann. 1943. Untersuchungen über Organextrakte zur Kenntnis der unverseifbaren Lipoide aus arteriosklerotischen Aorten. Helv. Chim. Acta. 26:2205–2221.CrossRefGoogle Scholar
  28. 28.
    Kantiengar, N.L. and R. A. Morton. 1955. Cholesta-3;5-dien-7-one in human atherosclerotic aortas. Biochem. J. 60:25–28.PubMedGoogle Scholar
  29. 29.
    Brooks, C.J. W., W. A. Harland, G. Steel. 1966. Squalene, 26-hydroxycholesterol and 7-ketocholesterol in human atheromatous plaques. Biochem. Biophys. Acta. 125:620–622.PubMedCrossRefGoogle Scholar
  30. 30.
    Kandutsch, A.A., H. W. Chen. 1973. Inhibition of sterol synthesis in cultured mouse cells by 7α-hydroxycholesterol, 7β-hydroxycholesterol, and 7-ketocholesterol. J. Biol. Chem. 248:8408–8417.PubMedGoogle Scholar
  31. 31.
    Brown, M.S., and J.L. Goldstein. 1974. Suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and inhibition of growth of human fibroblasts by 7-ketocholesterol. J. Biol. Chem. 249:7306–7314.PubMedGoogle Scholar
  32. 32.
    Brown, M.S., J.R. Faust, and J.L. Goldstein. 1975. Role of the low density lipoprotein receptor in regulating the content of free and esterified cholesterol in human fibroblasts. J. Clin. Invest. 55:783–793.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1976

Authors and Affiliations

  • R. J. Bing
    • 1
    • 2
  • J. S. M. Sarma
    • 1
    • 2
  • R. Fischer
    • 1
    • 2
  • S. Ikeda
    • 1
    • 2
  1. 1.Huntington Memorial HospitalPasadenaUSA
  2. 2.University of Southern CaliforniaLos Angeles, PasadenaUSA

Personalised recommendations