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. 1981 Oct;68(4):1003–1011. doi: 10.1172/JCI110322

Utilization of arachidonic and linoleic acids by cultured human endothelial cells.

A A Spector, T L Kaduce, J C Hoak, G L Fry
PMCID: PMC370887  PMID: 6793627

Abstract

When cultured human umbilical vein endothelial cells are supplemented with linoleic acid, the arachidonic acid content of the cellular phospholipids is reduced approximately 35%. Most of the fatty acid compositional change occurs during the first 24 h. One factor responsible for this effect is the inability of the endothelial cells to convert appreciable amounts of linoleic to arachidonic acid, due to a fatty acid delta 6-desaturase deficiency. By contrast, these endothelial cultures contain delta 5- and delta 9-desaturase activity and are able to elongate long-chain polyunsaturated fatty acids. The other factor that contributes to the decrease in arachidonic acid is that high concentrations of linoleic acid reduce the incorporation of arachidonate into cellular phospholipids. Stearic acid, a long-chain saturate, does not produce any reduction, whereas eicosatrienoic acid is an even more effective inhibitor than linoleic acid. In spite of the fact that high concentrations of these polyunsaturates produced inhibition, the endothelial cells were found to efficiently incorporate exogenous arachidonic acid into cellular phospholipids and triglycerides. This may serve to compensate for the inability of these cells to synthesize arachidonic acid from linoleic acid. These findings suggest that the endothelium obtains arachidonic acid from an extracellular source, that this cannot be provided in the form of linoleic acid and, in fact, that high concentrations of linoleic acid actually may interfere with the ability of the endothelium to maintain an adequate supply of intracellular arachidonic acid.

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Selected References

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

  1. Aeberhard E. E., Corbo L., Menkes J. H. Polyenoic acid metabolism in cultured human skin fibroblasts. Lipids. 1978 Nov;13(11):758–767. doi: 10.1007/BF02533473. [DOI] [PubMed] [Google Scholar]
  2. Bernert J. T., Jr, Sprecher H. Studies to determine the role rates of chain elongation and desaturation play in regulating the unsaturated fatty acid composition of rat liver lipids. Biochim Biophys Acta. 1975 Sep 19;398(3):354–363. doi: 10.1016/0005-2760(75)90186-1. [DOI] [PubMed] [Google Scholar]
  3. Bills T. K., Smith J. B., Silver M. J. Selective release of archidonic acid from the phospholipids of human platelets in response to thrombin. J Clin Invest. 1977 Jul;60(1):1–6. doi: 10.1172/JCI108745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chalvardjian A., Rudnicki E. Determination of lipid phosphorus in the nanomolar range. Anal Biochem. 1970 Jul;36(1):225–226. doi: 10.1016/0003-2697(70)90352-0. [DOI] [PubMed] [Google Scholar]
  5. Czervionke R. L., Hoak J. C., Fry G. L. Effect of aspirin on thrombin-induced adherence of platelets to cultured cells from the blood vessel wall. J Clin Invest. 1978 Oct;62(4):847–856. doi: 10.1172/JCI109197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Heimberg M., Dunn G. D., Wilcox G. The derivation of plasma-free fatty acids from dietary neutral fat in man. J Lab Clin Med. 1974 Mar;83(3):393–402. [PubMed] [Google Scholar]
  8. Hoak J. C., Czervionke R. L., Lewis L. J. Uptake and utilization of free fatty acids (FFA) by human endothelial cells. Thromb Res. 1974 Jun;4(6):879–883. doi: 10.1016/0049-3848(74)90030-9. [DOI] [PubMed] [Google Scholar]
  9. Hong S. L., Patton G., Deykin D. Arachidonic acid level in cellular lipids determines the amount of prostaglandins synthesized during cell growth in tissue culture. Prostaglandins. 1979 Jan;17(1):53–59. doi: 10.1016/0090-6980(79)90074-1. [DOI] [PubMed] [Google Scholar]
  10. Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. KAYDEN H. J., KARMEN A., DUMONT A. ALTERATIONS IN THE FATTY ACID COMPOSITION OF HUMAN LYMPH AND SERUM LIPOPROTEINS BY SINGLE FEEDINGS. J Clin Invest. 1963 Sep;42:1373–1381. doi: 10.1172/JCI104821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LANDS W. E., HART P. METABOLISM OF GLYCEROLIPIDS. VI. SPECIFICITIES OF ACYL COENZYME A: PHOSPHOLIPID ACYLTRANSFERASES. J Biol Chem. 1965 May;240:1905–1911. [PubMed] [Google Scholar]
  13. Lambremont E. N., Lee T. C., Blank M. L., Snyder F. delta5 desaturation of fatty acids in L-M cells. Biochem Biophys Res Commun. 1978 Feb 28;80(4):813–818. doi: 10.1016/0006-291x(78)91317-7. [DOI] [PubMed] [Google Scholar]
  14. Lees M. B., Paxman S. Modification of the Lowry procedure for the analysis of proteolipid protein. Anal Biochem. 1972 May;47(1):184–192. doi: 10.1016/0003-2697(72)90291-6. [DOI] [PubMed] [Google Scholar]
  15. Lowry R. R., Tinsley I. J. Rapid colorimetric determination of free fatty acids. J Am Oil Chem Soc. 1976 Jul;53(7):470–472. doi: 10.1007/BF02636814. [DOI] [PubMed] [Google Scholar]
  16. Ludwig S. A., Sprecher H. Substrate specificity studies on the malonyl-CoA-dependent chain elongation of all-cis polyunsaturated fatty acids by rat liver microsomes. Arch Biochem Biophys. 1979 Oct 1;197(1):333–341. doi: 10.1016/0003-9861(79)90253-4. [DOI] [PubMed] [Google Scholar]
  17. MORRISON W. R., SMITH L. M. PREPARATION OF FATTY ACID METHYL ESTERS AND DIMETHYLACETALS FROM LIPIDS WITH BORON FLUORIDE--METHANOL. J Lipid Res. 1964 Oct;5:600–608. [PubMed] [Google Scholar]
  18. Maeda M., Doi O., Akamatsu Y. Metabolic conversion of polyunsaturated fatty acids in mammalian cultured cells. Biochim Biophys Acta. 1978 Aug 25;530(2):153–164. [PubMed] [Google Scholar]
  19. Marcus A. J., Weksler B. B., Jaffe E. A. Enzymatic conversion of prostaglandin endoperoxide H2 and arachidonic acid to prostacyclin by cultured human endothelial cells. J Biol Chem. 1978 Oct 25;253(20):7138–7141. [PubMed] [Google Scholar]
  20. Mathers L., Bailey M. J. Enzyme deletions and essential fatty acid metabolism in cultured cells. J Biol Chem. 1975 Feb 10;250(3):1152–1153. [PubMed] [Google Scholar]
  21. McGee R., Spector A. A. Short-term effects of free fatty acids on the regulation of fatty acid biosynthesis in Ehrlich ascites tumor cells. Cancer Res. 1974 Dec;34(12):3355–3362. [PubMed] [Google Scholar]
  22. Nichaman M. Z., Sweeley C. C., Olson R. E. Plasma fatty acids in normolipemic and hyperlipemic subjects during fasting and after linoleate feeding. Am J Clin Nutr. 1967 Oct;20(10):1057–1069. doi: 10.1093/ajcn/20.10.1057. [DOI] [PubMed] [Google Scholar]
  23. Nordøy A., Svensson B., Hoak J. C. The effects of albumin bound fatty acids on the platelet inhibitory function of human endothelial cells. Eur J Clin Invest. 1979 Feb;9(1):5–10. doi: 10.1111/j.1365-2362.1979.tb01661.x. [DOI] [PubMed] [Google Scholar]
  24. Pande S. V., Mead J. F. Long chain fatty acid activation in subcellular preparations from rat liver. J Biol Chem. 1968 Jan 25;243(2):352–361. [PubMed] [Google Scholar]
  25. Shepherd J., Packard C. J., Grundy S. M., Yeshurun D., Gotto A. M., Jr, Taunton O. D. Effects of saturated and polyunsaturated fat diets on the chemical composition and metabolism of low density lipoproteins in man. J Lipid Res. 1980 Jan;21(1):91–99. [PubMed] [Google Scholar]
  26. Shepherd J., Packard C. J., Patsch J. R., Gotto A. M., Jr, Taunton O. D. Effects of dietary polyunsaturated and saturated fat on the properties of high density lipoproteins and the metabolism of apolipoprotein A-I. J Clin Invest. 1978 Jun;61(6):1582–1592. doi: 10.1172/JCI109078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Skipski V. P., Peterson R. F., Barclay M. Quantitative analysis of phospholipids by thin-layer chromatography. Biochem J. 1964 Feb;90(2):374–378. doi: 10.1042/bj0900374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Spector A. A., Hoak J. C., Fry G. L., Denning G. M., Stoll L. L., Smith J. B. Effect of fatty acid modification on prostacyclin production by cultured human endothelial cells. J Clin Invest. 1980 May;65(5):1003–1012. doi: 10.1172/JCI109752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Spector A. A., Kiser R. E., Denning G. M., Koh S. W., DeBault L. E. Modification of the fatty acid composition of cultured human fibroblasts. J Lipid Res. 1979 May;20(4):536–547. [PubMed] [Google Scholar]
  30. Weksler B. B., Marcus A. J., Jaffe E. A. Synthesis of prostaglandin I2 (prostacyclin) by cultured human and bovine endothelial cells. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3922–3926. doi: 10.1073/pnas.74.9.3922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yavin E., Yavin Z., Menkes J. H. Polyunsaturated fatty acid metabolism in neuroblastoma cells in culture. J Neurochem. 1975 Jan;24(1):71–77. doi: 10.1111/j.1471-4159.1975.tb07630.x. [DOI] [PubMed] [Google Scholar]

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