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. 1968 Mar;47(3):595–603. doi: 10.1172/JCI105755

Sterol synthesis in the human arterial intima

Aram V Chobanian 1,2,3
PMCID: PMC297205  PMID: 5637146

Abstract

Intimal sterol synthesis was examined in isolated human arterial segments obtained at surgery or at postmortem examination. The tissues were incubated with acetate-1-14C and mevalonate-2-14C and the incorporation of these precursors into sterols was determined. Intimal sterols were isolated by multiple chromatographic techniques and purified by bromination and oxidation procedures. The results indicate that the arterial intima can incorporate acetate and mevalonate into cholesterol, cholestanol, and squalene. Cholestanol was the major sterol synthesized by the arterial wall, but cholesterol production was also consistently observed. The findings suggest that local synthesis is a potential source of sterol accumulation within the arterial wall.

The conversion of cholesterol to other sterols was also studied in terminally ill patients receiving labeled cholesterol before death. Tissue analyses revealed the presence of labeled cholestanol as well as cholesterol in the tissue 5-104 days after labeled cholesterol administration. The results demonstrate the conversion of cholesterol to cholestanol in man and suggest that the exchange of cholestanol between the blood and tissues is similar to that of cholesterol.

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Selected References

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

  1. AVIGAN J., GOODMAN D. S., STEINBERG D. THIN-LAYER CHROMATOGRAPHY OF STEROLS AND STEROIDS. J Lipid Res. 1963 Jan;4:100–101. [PubMed] [Google Scholar]
  2. AZARNOFF D. L. Species differences in cholesterol biosynthesis by arterial tissue. Proc Soc Exp Biol Med. 1958 Aug-Sep;98(4):680–683. doi: 10.3181/00379727-98-24150. [DOI] [PubMed] [Google Scholar]
  3. BIGGS M. W., KRITCHEVSKY D., COLMAN D., GOFMAN J. W., JONES H. B., LINDGREN F. T., HYDE G., LYON T. P. Observations on the fate of ingested cholesterol in man. Circulation. 1952 Sep;6(3):359–366. doi: 10.1161/01.cir.6.3.359. [DOI] [PubMed] [Google Scholar]
  4. BOTTCHER C. J., WOODFORD F. P., ter HAAR ROMENY-WACHTER C., BOELSMA-VAN HOUTE E., van GENT C. Fatty-acid distribution in lipids of the aortic wall. Lancet. 1960 Jun 25;1(7139):1378–1383. doi: 10.1016/s0140-6736(60)91153-3. [DOI] [PubMed] [Google Scholar]
  5. CHAIKOFF I. L., CHAPMAN D. D., HAROLD F. M. Metabolism of cholestanol. I. Fate of cholestanol-4-C14 in the rat. II. Metabolic interrelations of cholestanol, epicholesterol, and delta4-cholestenone. J Biol Chem. 1957 Jan;224(1):609–620. [PubMed] [Google Scholar]
  6. CHOBANIAN A. V., HOLLANDER W. Body cholesterol metabolism in man. I. The equilibration of serum and tissue cholesterol. J Clin Invest. 1962 Sep;41:1732–1737. doi: 10.1172/JCI104631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. CHOBANIAN A. V., HOLLANDER W. TISSUE DISTRIBUTION OF CHOLESTEROL AND 24-DEHYDROCHOLESTEROL DURING CHRONIC TRIPARANOL THERAPY. J Lipid Res. 1965 Jan;6:37–42. [PubMed] [Google Scholar]
  8. Chobanian A. V., Hollander W. Phospholipid synthesis in the human arterial intima. J Clin Invest. 1966 Jun;45(6):932–938. doi: 10.1172/JCI105408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DALY M. M., DEMING Q. B., RAEFF V. M., BRUN L. M. CHOLESTEROL CONCENTRATION AND CHOLESTEROL SYNTHESIS IN AORTAS OF RATS WITH RENAL HYPERTENSION. J Clin Invest. 1963 Oct;42:1606–1612. doi: 10.1172/JCI104845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DAYTON S. Turnover of cholesterol in the artery walls of normal chickens. Circ Res. 1959 May;7(3):468–475. doi: 10.1161/01.res.7.3.468. [DOI] [PubMed] [Google Scholar]
  11. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  12. FRANTZ I. D., Jr CHROMATOGRAPHY OF UNESTERIFIED STEROLS ON SILICIC ACID-SUPER-CEL. J Lipid Res. 1963 Apr;4:176–178. [PubMed] [Google Scholar]
  13. GOODMAN D. S. SQUALENE IN HUMAN AND RAT BLOOD PLASMA. J Clin Invest. 1964 Jul;43:1480–1485. doi: 10.1172/JCI105024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. MOSBACH E. H., BLUM J., ARROYO E., MILCHS A new method for the determination of dihydrocholesterol in tissues. Anal Biochem. 1963 Feb;5:158–169. doi: 10.1016/0003-2697(63)90022-8. [DOI] [PubMed] [Google Scholar]
  15. NEWMAN H. A., ZILVERSMIT D. B. Quantitative aspects of cholesterol flux in rabbit atheromatous lesions. J Biol Chem. 1962 Jul;237:2078–2084. [PubMed] [Google Scholar]
  16. NICHOLS C. W., Jr, LINDSAY S., CHAIKOFF I. L. Production of arteriosclerosis in birds by the prolonged feeding of dihydrocholesterol. Proc Soc Exp Biol Med. 1955 Aug;89(4):609–613. doi: 10.3181/00379727-89-21891. [DOI] [PubMed] [Google Scholar]
  17. ROSENFELD R. S., HELLMAN L. The biochemical transformation of cholestenone to cholesterol. J Biol Chem. 1958 Nov;233(5):1089–1092. [PubMed] [Google Scholar]
  18. Robertson A. L., Jr Transport of plasma lipoproteins and ultrastructure of human arterial intimacytes in culture. Wistar Inst Symp Monogr. 1967;6:115–128. [PubMed] [Google Scholar]
  19. Rosenfeld R. S., Zumoff B., Hellman L. Conversion of cholesterol injected into man to cholestanol via a 3-ketonic intermediate. J Lipid Res. 1967 Jan;8(1):16–23. [PubMed] [Google Scholar]
  20. SCHWENK E., WERTHESSEN N. T. Studies on the biosynthesis of cholesterol. III. Purification of C14-cholesterol from perfusions of livers and other organs. Arch Biochem Biophys. 1952 Oct;40(2):334–341. doi: 10.1016/0003-9861(52)90119-7. [DOI] [PubMed] [Google Scholar]
  21. SHEFER S., MILCH S., MOSBACH E. H. BIOSYNTHESIS OF 5-ALPHA-CHOLESTAN-3-BETA-OL IN RAT AND GUINEA PIG LIVER IN VITRO. J Lipid Res. 1965 Jan;6:33–36. [PubMed] [Google Scholar]
  22. SIPERSTEIN M. D., CHAIKOFF I. L., CHERNICK S. S. Significance of endogenous cholesterol in arteriosclerosis; synthesis in arterial tissue. Science. 1951 Jun 29;113(2948):747–749. doi: 10.1126/science.113.2948.747. [DOI] [PubMed] [Google Scholar]
  23. TRUSWELL A. S., MITCHELL W. D. SEPARATION OF CHOLESTEROL FROM ITS COMPANIONS, CHOLESTANOL AND DELTA-7-CHOLESTENOL, BY THIN-LAYER CHROMATOGRAPHY. J Lipid Res. 1965 Jul;6:438–441. [PubMed] [Google Scholar]
  24. VAHOUNY G. V., MAYER R. M., ROE J. H., TREADWELL C. R. Determination of 3-beta-hydroxy sterols with anthrone reagent. Arch Biochem Biophys. 1960 Feb;86:210–214. doi: 10.1016/0003-9861(60)90406-9. [DOI] [PubMed] [Google Scholar]
  25. WERBIN H., CHAIKOFF I. L., IMADA M. R. 5alpha Cholestan-3beta-ol: its distribution in tissues and its synthesis from cholesterol in the guinea pig. J Biol Chem. 1962 Jul;237:2072–2077. [PubMed] [Google Scholar]
  26. WERTHESSEN N. T., MILCH L. J., REDMOND R. F., SMITH L. L., SMITH E. C. Biosynthesis and concentration of cholesterol by the intact surviving bovine aorta in vitro. Am J Physiol. 1954 Jul;178(1):23–29. doi: 10.1152/ajplegacy.1954.178.1.23. [DOI] [PubMed] [Google Scholar]

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