The Role of Linoleic Acid in Endothelial Cell Gene Expression

Relationship to Atherosclerosis
  • Michal Toborek
  • Bernhard Hennig
Part of the Subcellular Biochemistry book series (SCBI, volume 30)


Although the mortality from coronary heart disease has declined recently, atherosclerosis and related vascular disorders still are the leading causes of death in the United States and other Western countries. The etiology of this disease is multifactorial, with hyperlipidemia, smoking, diabetes mellitus, hypertension, and obesity being well-established risk factors for the development of atherosclerosis. Dietary fat affects plasma lipids and lipoproteins and thus is linked to atherosclerosis (Watkins et al., 1996). Injury to or abnormal mechanisms of the vascular endothelium may be initiating events in the etiology of atherosclerosis.


Endothelial Cell Linoleic Acid Heparan Sulfate Proteoglycan Chondroitin Sulfate Proteoglycan Cellular Oxidative Stress 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Baeuerle, P. A., 1991, The inducible transcription activator NF-xB: Regulation by distinct protein subunits, Biochim. Biophys. Acta 1072:63–80.PubMedGoogle Scholar
  2. Barath, P., Fishbein, M. C., Cao, J., Berenson, J., Helfant, R. H., and Forrester, J. S., 1990, Detection and localization of tumor necrosis factor in human atheroma, Am. J. Cardiol. 65:297–302.PubMedCrossRefGoogle Scholar
  3. Barnes, P. J., and Karin, M., 1997, Nuclear factor-xB. A pivotal transcription factor in chronic inflammatory diseases, N. Engl. J. Med. 336:1066–1071.PubMedCrossRefGoogle Scholar
  4. Beaver, J. P., and Waring, P., 1995, A decrease in intracellular glutathione concentration precedes the onset of apoptosis in murine thymocytes, Eur. J. Cell Bioi 68:47–54.Google Scholar
  5. Berliner, J. A., Navab, M., Fogelman, A. M., Frank, J. S., Demer, L. L., Edwards, P. A., Watson, A. D., and Lusis, A. J., 1995, Atherosclerosis: Basic mechanisms. Oxidation, inflammation, and genetics, Circulation 91:2488–2496.PubMedCrossRefGoogle Scholar
  6. Beyaert, R., and Fiers, W., 1994, Molecular mechanisms of tumor necrosis factor-induced cytotoxicity. What we do understand and what we do not, FEBS Lett. 340:9–16.PubMedCrossRefGoogle Scholar
  7. Bjorkerud, B., and Bjorkerud, S., 1996, Contrary effects of lightly and strongly oxidized LDL with potent promotion of growth versus apoptosis on arterial smooth muscle cells, macrophages, and fibroblasts, Arterioscler. Thromb. Vasc. Biol. 16:416–424.PubMedCrossRefGoogle Scholar
  8. Camacho, M., Godessart, N., Anton, R., Garcia, M., and Vila, L., 1995, Interleukin-1 enhances the ability of cultured human umbilical vein endothelial cells to oxidize linoleic acid, J. Biol. Chem. 270:17279–17286.PubMedCrossRefGoogle Scholar
  9. Chatelain, P., Laurel, R., and Gillard, M., 1985, Effect of amiodarone on membrane fluidity and Na+/K+ ATPase activity in rat-brain synaptic membranes, Biochem. Biophys. Res. Commun. 129:148–154.PubMedCrossRefGoogle Scholar
  10. Collins, T., Read, M. A., Neish, A. S., Whitley, M. Z., Thanos, D., and Maniatis, T., 1995, Transcriptional regulation of endothelial cell adhesion molecules: NF-xB and cytokine-inducible enhancers, FASEB J. 9:899–909.PubMedGoogle Scholar
  11. De Caterina, R., and Libby, P., 1996, Control of endothelial leukocyte adhesion molecules by fatty acids, Lipids 31:S57–S63.PubMedCrossRefGoogle Scholar
  12. Denke, M. A., and Grundy, S. M., 1992, Comparison of effects of lauric and palmitic acid on plasma lipids and lipoproteins, Am. J. Clin. Nutr. 56:895–898.PubMedGoogle Scholar
  13. Esterbauer, H., 1993, Cytotoxicity and genotoxicity of lipid-oxidation products, Am. J. Clin. Nutr. 57:779S–786S.PubMedGoogle Scholar
  14. Farach, M. C., Tang, J. P., Decke, G. L., and Carson, D. D., 1987, Heparin/heparan sulfate is involved in attachment and spreading of mouse embryos in vitro, Dev. Biol. 123:401–410.PubMedCrossRefGoogle Scholar
  15. Folcik, V. A., and Cathcart, M. K., 1994, Predominance of esterified hydroperoxy-linoleic acid in human monocyte-oxidized LDL, J. Lipid Res. 35:1570–1582.PubMedGoogle Scholar
  16. Fransson, L. A., Carlstedt, I., Coster, L., and Malmstrom, A., 1983, Proteoheparan sulfate from human skin fibroblasts. Evidence for self-interaction via the heparan sulfate side chains, J. Biol. Chem. 258:14342–14345.PubMedGoogle Scholar
  17. Fujiwara, S., Wiedemann, H., Timpl, R., Lustig, A., and Engel, J., 1984, Structure and interactions of heparan sulfate proteoglycans from a mouse tumor basement membrane, Eur. J. Biochem. 143:145–157.PubMedCrossRefGoogle Scholar
  18. Graber, R., Sumida, C., and Nunez, E.A., 1994, Fatty acids and cell signal transduction, J. Lipid Med. 9:91–116.Google Scholar
  19. Grimble, R. F., 1996, Interaction between nutrients, pro-inflammatory cytokines and inflammation, Clin. Sci. 91:121–130.PubMedGoogle Scholar
  20. Hassell, J. R., Kimura, J. H., and Hascall, V. C., 1986, Proteoglycan core protein families, Annu. Rev. Biochem. 55:539–567.PubMedCrossRefGoogle Scholar
  21. Haudenshild, C. C., 1990, Pathogenesis of atherosclerosis: state of the art, Cardiovasc. Drugs Ther. 4:993–1004.CrossRefGoogle Scholar
  22. Hayakawa, M., Ishida, N., Takeuchi, K., Shibamoto, S., Hori, T., Oku, N., Ito, F., and Tsujimoto, M. J., 1993, Arachidonic acid-selective cytosolic phospholipase A2 is crucial in the cytotoxic action of tumor necrosis factor, J. Biol. Chem. 268:11290–11295.PubMedGoogle Scholar
  23. Hegsted, D. M., McGandy, R. B., Myers, M. L., and Stare, F. J., 1965, Quantitative effects of dietary fat on serum cholesterol in man, Am. J. Clin. Nutr. 17:281–295.PubMedGoogle Scholar
  24. Hegsted, D. M., Ausman, L. M., Johnson, J. A., and Dallal, G. E., 1993, Dietary fat and serum lipids: An evaluation of the experimental data, Am. J. Clin. Nutr. 57:875–883.PubMedGoogle Scholar
  25. Hennig, B., Shasby, D. M., Fulton, A. B., and Spector, A. A., 1984, Exposure to free fatty acid increases the transfer of albumin across cultured endothelial monolayers, Arteriosclerosis 4:489–497.PubMedCrossRefGoogle Scholar
  26. Hennig, B., Shasby, D. M., and Spector, A. A., 1985, Exposure to fatty acid increases human low density lipoprotein transfer across cultured endothelial monolayers, Circ. Res. 57:776–780.PubMedCrossRefGoogle Scholar
  27. Hennig, B., Enoch, C., and Chow, C. K., 1986, Linoleic acid hydroperoxide increases the transfer of albumin across cultured endothelial monolayers, Arch. Biochem. Biophys. 248:353–357.PubMedCrossRefGoogle Scholar
  28. Hennig, B., Enoch, C., and Chow, C. K., 1987, Protection by vitamin E against endothelial cell injury by linoleic acid hydroperoxides, Nutr. Res. 7:1253–1260.CrossRefGoogle Scholar
  29. Hennig, B., Alvarado, A., Ramasamy, S., Boissonneault, G. A., Decker, E., and Means, W. J., 1990, Fatty acid induced disruption of endothelial barrier function in culture, Biochem. Arch. 6:409–417.Google Scholar
  30. Hennig, B., Ramasamy, S., Alvarado, A., Shantha, N. C., Boissonneault, G. A., Decker, E. A., and Watkins, B. A. 1993, Selective disruption of endothelial barrier function in culture by pure fatty acids and fatty acids derived from animal and plant fats, J. Nutr. 123:1208–1216.PubMedGoogle Scholar
  31. Hennig, B., Lipke, D. W., Boissonneault, G. A., and Ramasamy, S., 1995, Role of fatty acids and eicosanoids in modulating proteoglycan metabolism in endothelial cells, Prostaglandins Leukotrienes Essential Fatty Acids 53:315–324.CrossRefGoogle Scholar
  32. Hennig, B., Toborek, M., Joshi-Barve, S., Barger, S. W., Barve, S., Mattson, M. P., and McClain, C. J., 1996a, Linoleic acid activates NF-xB and induces NF-xB-dependent transcription in cultured endothelial cells, Am. J. Clin. Nutr. 63:322–328.PubMedGoogle Scholar
  33. Hennig B., Toborek, M., McClain, C. J., and Diana, J. N., 1996b, Nutritional implications in vascular endothelial cell metabolism, J. Am. Coll. Nutr. 15:345–358.PubMedGoogle Scholar
  34. Hodgson, J. M., Wahlqvist, M. L., Boxall, J. A., and Balazs, N. D., 1993, Can linoleic acid contribute to coronary artery disease? Am. J. Clin. Nutr. 58:228–234.PubMedGoogle Scholar
  35. Janero, D. R., 1991, Therapeutic potential of vitamin E in the pathogenesis of spontaneous atherosclerosis, Free Radic. Biol. Med. 11:129–144.PubMedCrossRefGoogle Scholar
  36. Jolies, P., ed., 1994, Proteoglycans, Birkhauser, Basel.Google Scholar
  37. Khan, B. V., Parthasarathy, S. S., Alexander, R. W., and Medford, R. M., 1995, Modified low density lipoprotein and its constituents augment cytokine-activated vascular cell adhesion molecule-1 gene expression in human vascular endothelial cells, J. Clin. Invest. 95:1262–1270.PubMedCrossRefGoogle Scholar
  38. Kim, D. N., Eastman, A., Baker, J. E., Mastrangelo, A., Sethi, S., Ross, J. S., Schmee, J., and Thomas, W. A., 1995, Fish oil, atherosclerosis, and thrombogenesis, Ann. N. Y. Acad. Sci. USA 748:474–480.CrossRefGoogle Scholar
  39. Kleinman, H. K., McGarvey, M. L., Hassell, J. R., and Martin, G. R., 1983, Formation of a supramolecular complex is involved in the reconstitution of basement membrane components, Biochemistry 22:4969–4974.PubMedCrossRefGoogle Scholar
  40. Koide, M., Kawahara, Y., Tsuda, T., Ishida, Y., Shii, K., and Yokoyama, M., 1992, Endothelin-1 stimulates tyrosine phosphorylation and the activities of two mitogen-activated protein kinases in cultured vascular muscle cells, J. Hypertens. 10:1173–1182.PubMedCrossRefGoogle Scholar
  41. Kok, F. J., van Poppel, G., Meise, J., Verheul, E., Schouten, E. G., Kruyssen, D. H. C. M., and Hofman, A., 1991, Do antioxidants and polyunsaturated fatty acids have a combined association with coronary atherosclerosis? Atherosclerosis 31:85–90.CrossRefGoogle Scholar
  42. Kühn, H., Belkner, J., Zaiss, S., Fahrenklemper, T., and Wohlfeil, S., 1994, Involvement of 15-lipoxygenase in early stages of atherogenesis, J. Exp. Med. 179:1903–1911.PubMedCrossRefGoogle Scholar
  43. Lark, M. W., and Culp, L. A., 1984, Turnover of heparan sulfate proteoglycans from substratum adhesion sites of murine fibroblasts, J. Biol Chem. 259:212–217.PubMedGoogle Scholar
  44. Louheranta, A. M., Porkkala-Sarataho, E. K., Nyyssonen, M. K., Salonen, R. M., and Salonen, J. T., 1993, Linoleic acid intake and susceptibility of very low density and low density lipoproteins to oxidation in men, Am. J. Clin. Nutr. 63:698–703.Google Scholar
  45. Loustarinen, R., Boberg, M., and Saldeen, T., 1993, Fatty acid composition in total phospholipids of human coronary arteries in sudden cardiac death, Atherosclerosis 99:187–193.CrossRefGoogle Scholar
  46. Mattson, M. P., Barger, S. W., Begley, J. G., and Mark, R. J., 1995, Calcium, free radicals, and excitotoxic neuronal death in primary cell culture, Meth. Cell. Biol. 46:187–215.CrossRefGoogle Scholar
  47. Maziere, C., Auclair, M., and Maziere, J. C., 1994, Tumor necrosis factor enhances low density lipoprotein oxidative modification by monocytes and endothelial cells, FEBS Lett. 338:43–46.PubMedCrossRefGoogle Scholar
  48. McConkey, D. J., and Orrenius, S., 1996, The role of calcium in the regulation of apoptosis, J. Leukocyte. Biol. 59:775–83.PubMedGoogle Scholar
  49. Mensink, R. P., 1993, Effects of the individual saturated fatty acids on serum lipids and lipoprotein concentrations, Am. J. Clin. Nutr. 57:711S–714S.PubMedGoogle Scholar
  50. Munro, J. M., and Cotran, R. S., 1988, The pathogenesis of atherosclerosis: Atherogenesis and inflammation, Lab. Invest. 58:249–261.PubMedGoogle Scholar
  51. Ng, T. K. W., Hayes, K. C., DeWitt, G. F., Jegathesan, M., Satgunasingam, N., Ong, A. S. H., and Tan, D., 1992, Dietary palmitic and oleic acids exert similar effects on serum cholesterol and lipoprotein profiles in normocholesterolemic men and women, J. Am. Coll. Nutr. 11:383–390.PubMedGoogle Scholar
  52. Olgemoller, B., Schleicher, E. D., Schwaabe, S., Guretzki, H. J., and Gerbitz, K. D., 1990, High concentrations of low density lipoprotein decrease basement membrane-associated heparan sulfate proteoglycan in cultured endothelial cells, FEBS Lett, 264:37–39.PubMedCrossRefGoogle Scholar
  53. Parhami, F., Fang, Z. T., Fogelman, A. M., Andalibi, A., Territo, M. C., and Berliner, J. A., 1993, Minimally modified low density lipoprotein-induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate, J. Clin. Invest. 92:471–478.PubMedCrossRefGoogle Scholar
  54. Pietsch, A., Weber, C., Goretzki, M., Weber, P. C., and Lorenz, R. L., 1995, N-3 but not N-6 fatty acids reduce the expression of the combined adhesion and scavenger receptor CD 36 in human monocyte cells, Cell Biochem. Funct. 13:211–216.PubMedCrossRefGoogle Scholar
  55. Radhakrishnamurthy, B., Srinivasan, S. R., Vijayagopal, P., and Berenson, G. S., 1990, Arterial wall proteoglycans—Biological properties related to pathogenesis of atherosclerosis, Eur. Heart J. 11(Suppl. E):148–157.PubMedCrossRefGoogle Scholar
  56. Ramasamy, S., Boissonneault, G. A., Lipke, D. W., and Hennig, B., 1993, Proteoglycans and endothelial barrier function: Effect of linoleic acid exposure to porcine pulmonary artery endothelial cells, Atherosclerosis 103:279–290.PubMedCrossRefGoogle Scholar
  57. Ramasamy, S., Lipke, D. W., McClain, C. J., and Hennig, B., 1995, Tumor necrosis factor reduces proteoglycan synthesis in cultured endothelial cells, J. Cell Physiol. 162:119–126.PubMedCrossRefGoogle Scholar
  58. Rao, G. N., Alexander, R. W., and Runge, M. S., 1995, Linoleic acid and its metabolites, hydroperoxyoctadecadienoic acids, stimulate c-Fos, c-Jun, and c-Myc mRNA expression, mitogen-activated protein kinase activation, and growth in rat aortic smooth muscle cells, J. Clin. Invest. 96:842–847.PubMedCrossRefGoogle Scholar
  59. Read, M. A., Neish, A. S., Luscinskas, F. W., Palombella, V. J., Maniatis, T., and Collins, T., 1995, The proteasome pathway is required for cytokine-induced endothelial-leukocyte adhesion molecule expression, Immunity 2:493–506.PubMedCrossRefGoogle Scholar
  60. Renier, G., Olivier, M., Skamene, E., and Radzioch, D., 1994a, Induction of tumor necrosis factor alpha gene expression by lipoprotein lipase requires protein kinase C activation, J. Lipid Res. 35:1413–1421.Google Scholar
  61. Renier, G., Skamene, E., DeSanctis, J. B., and Radzioch, D., 1994b, Induction of tumor necrosis factor a gene expression by lipoprotein lipase, J. Lipid Res. 35:271–278.PubMedGoogle Scholar
  62. Ridker, P. M., Cushman, M., Stampfer, M. J., Tracy, R. P., and Hennekens, C. H., 1997, Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men, N. Engl. J. Med. 336:973–979.PubMedCrossRefGoogle Scholar
  63. Ross, R., 1986, The pathogenesis of atherosclerosis—An update, N. Engl. J. Med. 314:488–500.PubMedCrossRefGoogle Scholar
  64. Ruoslahti, E., 1988, Structure and biology of proteoglycans, Annu. Rev. Cell Biol. 4:229–255.PubMedCrossRefGoogle Scholar
  65. Rus, H. G., Niculescu, F., and Vlaicu, R., 1991, Tumor necrosis factor-alpha in human arterial wall with atherosclerosis, Atherosclerosis 89:247–254.PubMedCrossRefGoogle Scholar
  66. Sandstrom, P. A., Pardi, D., Tebbey, P. W., Dudek, R. W., Terrian, D. M., Folks, T. M., and Buttke, T. M., 1995, Lipid hydroperoxide-induced apoptosis: Lack of inhibition by Bcl-2 overexpression, FEBS Lett. 365:66–70.PubMedCrossRefGoogle Scholar
  67. Sato, N., Iwata, S., Nakamura, K., Hori, T., Mori, K., and Yodoi, J., 1995, Thiol-mediated redox regulation of apoptosis. Possible roles of cellular thiols other than glutathione in T cell apoptosis, J. Immunol. 154:3194–3203.PubMedGoogle Scholar
  68. Saunders, S., and Bernfield, M., 1987, Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as an interstitial matrix receptor, J. Cell Biol. 106:423–430.CrossRefGoogle Scholar
  69. Shakhov, A. N., Collart, M. A., Vassalli, P., Nedospasow, S. A., and Jongeneel, C. V., 1990, xB-Type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor a gene in primary macrophages, J. Exp. Med. 171:35–47.PubMedCrossRefGoogle Scholar
  70. Schreck, R., Albermann, K., and Baeuerle, P. A., 1992, Nuclear factor xB: An oxidative stress-responsive transcription factor of eukaryotic cells (A review), Free Radic. Res. Commun. 17:221–237.PubMedCrossRefGoogle Scholar
  71. Schulze-Osthoff, K., Bakker, A. C., Vanhaesebroeck, B., Beyaert, R., Jacob, W. A., and Fries, W., 1992, Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation, J. Biol. Chem. 267:5317–5323.PubMedGoogle Scholar
  72. Shirakawa, F., and Mizel, S. B., 1989, In vitro activation and nuclear translocation of NF-kappa B catalyzed by cyclic AMP-dependent protein kinase and protein kinase C, Mol. Cell. Biol. 9:2424–2430.PubMedGoogle Scholar
  73. Siebenlist, U., Franzoso, G., and Brown, K., 1994, Structure, regulation and function of NF-xB, Annu. Rev. Cell Biol. 10:405–455.PubMedCrossRefGoogle Scholar
  74. Siflinger-Birnboim, A., Schnitzer, J., Lum, H., Blumenstock, F. A., Shen, C.-P. J., Del Vecchio, P. J., and Malik, A. E., 1991, Lectin binding to gp60 decreases specific albumin binding and transport in pulmonary artery endothelial monolayers, J. Cell Physiol. 149:575–584.PubMedCrossRefGoogle Scholar
  75. Simionescu, M., and Simionescu, N., 1993, Proatherosclerotic events: Pathobiochemical changes occurring in the arterial wall before monocyte migration, FASEB J. 7:1359–1366.PubMedGoogle Scholar
  76. Slater, A. F., Nobel, C. S., and Orrenius, S., 1995, The role of intracellular oxidants in apoptosis, Biochem. Biophys. Acta 1271:59–62.PubMedCrossRefGoogle Scholar
  77. Steinberg, D., and Witztum, J. L., 1990, Lipoproteins and atherosclerosis, JAMA 264:3047–3052.PubMedCrossRefGoogle Scholar
  78. Tanaka, T., Hidaka, T., Ogura, R., and Sugiyama, M., 1988, Changes of membrane fluidity and Na+, K+-ATPase activity during cellular differentiation in the guinea pig epidermis, Arch. Dermatol. Res. 280:29–32.PubMedCrossRefGoogle Scholar
  79. Tanganelli, P., Bianciardi, G., Carducci, A., Palummo, N., Simoes, C., Tarabochia, B., Weber, G., Verzuri, M. S., and Auteri, A., 1992, Updating on in-vivo and in-vitro effects of heparin and other glycosaminoglycans (mesoglycan) on arterial endothelium: A morphometrical study, Int. J. Tiss. React. 14:149–153.Google Scholar
  80. Tartaglia, L. A., Rothe, M., Hu, Y.-F., and Goedde, D. V., 1993, Tumor necrosis factor’s cytotoxic activity is signaled by the p55 TNF receptor, Cell 73:213–216.PubMedCrossRefGoogle Scholar
  81. Templeton, D. M., 1992, Proteoglycans in cell regulation, Crit. Rev. Clin. Lab. Sci. 29:141–184.PubMedCrossRefGoogle Scholar
  82. Thanos, D., and Maniatis, T., 1995, NF-xB: A lesson in family values, Cell 80:529–532.PubMedCrossRefGoogle Scholar
  83. Toborek, M., and Hennig, B., 1994, Fatty acid-mediated effects on the glutathione redox cycle in cultured endothelial cells, Am. J. Clin. Nutr. 59:60–65.PubMedGoogle Scholar
  84. Toborek, M., Barger, S. W., Mattson, M. P., Barve, S., McClain, C. J., and Hennig, B., 1996, Linoleic acid and TNF-α cross-amplify oxidative injury and dysfunction of endothelial cells, J. Lipid Res. 37:123–135.PubMedGoogle Scholar
  85. Toborek, M., Kaiser, S., Mattson, M. P., and Hennig, B., 1997a, Fatty acid-mediated injury and endothelial cell autocrine TNF production, Atherosclerosis 134:284.Google Scholar
  86. Toborek, M., Blanc, E. M., Kaiser, S., Mattson, M. P., and Hennig, B., 1997b Linoleic acid potentiates TNF-mediated oxidative stress, disruption of calcium homeostasis and apoptosis of cultured vascular endothelial cells, J. Lipid Res. 38:2155–2147.PubMedGoogle Scholar
  87. Tracey, K. J., and Cerami, A., 1992, Tumor necrosis factor and regulation of metabolism in infection: Role of systemic versus tissue levels, Proc. Soc. Exp. Biol. Med. 200:233–239.PubMedCrossRefGoogle Scholar
  88. Vaddi, K., Nicolini, F. A., Mehta, P., and Mehta, J. L., 1994, Increased secretion of tumor necrosis factor-a and interferon-γ by mononuclear leukocytes in patients with ischemic heart disease. Relevance in Superoxide anion generation, Circulation 90:694–699.PubMedCrossRefGoogle Scholar
  89. Vijayagopal, P., Srinivasan, S. R., Dalferes, E. R., Radhakrishnamurthy, B., and Berenson, G. S., 1988, Effect of low density lipoproteins on the synthesis and secretion of proteoglycans by human endothelial cells in culture, Biochem. J. 255:639–646.PubMedGoogle Scholar
  90. Yam, D., Eliraz, A., and Berry, E. M., 1996, Diet and disease, the Israeli paradox: Possible dangers of a high omega-6 polyunsaturated fatty acid diet, Isr. J. Med. Sci. 32:1134–1143.PubMedGoogle Scholar
  91. Ylä-Herttuala, S., Rosenfed, M. E., Parthasarathy, S., Glass, C. K., Sigal, E., Witztum, J. T., and Steinberg, D., 1990, Colocalization of 15-Lipoxygenase mRNA and protein with epitopes of oxidized low density lipoprotein in macrophage-rich areas of atherosclerotic lesions, Proc. Natl. Acad. Sci. USA 87:6959–6963.PubMedCrossRefGoogle Scholar
  92. Ylä-Herttuala, S., Rosenfed, M. E., Parthasarathy, S., Sigal, E., Särkioia, T., Witztum, J. T., and Steinberg, D., 1991, Gene expression in macrophage-rich human atherosclerotic lesions. 15-Lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts, J. Clin. Invest. 87:1146–1152.PubMedCrossRefGoogle Scholar
  93. Wang, T., and Powell, W. S., 1991, Increased levels of monohydroxy metabolites of arachidonic acid and linoleic acid in LDL and aorta from atherosclerotic rabbits, Biochem. Biophys. Res. Commun. 1084:129–138.Google Scholar
  94. Wardle, E. N., 1994, Vascular permeability in diabetics and implications for therapy, Diabetes Res. Clin, Pract. 23:135–139.CrossRefGoogle Scholar
  95. Watkins, B. A., Hennig, B., and Toborek, M., 1996, Diet and health, in Bailey’s Industrial Oil and Fat Products, Vol. 1, Edible Oil and Fat Products: General Applications 5th ed. (Y. H. Hui, ed.), pp. 159–214, Wiley, New York.Google Scholar
  96. Wight, T. N. 1989, Cell biology of arterial proteoglycans, Arteriosclerosis 9:1–20.PubMedCrossRefGoogle Scholar
  97. Wight, N., Kinsella, M. G., and Potter-Perigo, S., 1985, Proteoglycans synthesized and secreted by cultured vascular cells, in Extracellular Matrix: Structure and Function (A. Riddi ed.), pp. 321–332, Alan R. Liss, New York.Google Scholar
  98. Wong, G. H., 1995, Protective roles of cytokines against radiation: Induction of mitochondrial MnSOD, Biochim. Biophys. Acta 1271:205–209.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Michal Toborek
    • 1
  • Bernhard Hennig
    • 2
  1. 1.Department of SurgeryUniversity of Kentucky Medical CenterLexingtonUSA
  2. 2.Department of Nutrition and Food ScienceUniversity of KentuckyLexingtonUSA

Personalised recommendations