Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Aug;94(2):592–600. doi: 10.1172/JCI117374

Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells.

R Faruqi 1, C de la Motte 1, P E DiCorleto 1
PMCID: PMC296135  PMID: 7518838

Abstract

Antioxidants have been proposed to be anti-atherosclerotic agents; however, the mechanisms underlying their beneficial effects are poorly understood. We have examined the effect of alpha-tocopherol (alpha-tcp) on one cellular event in atherosclerotic plaque development, monocyte adhesion to stimulated endothelial cells (ECs). Human umbilical vein ECs were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion: IL-1 (10 ng/ml), LPS (10 ng/ml), thrombin (30 U/ml), or PMA (10 nM). Agonist-induced monocytic cell adhesion, but not basal adhesion, was inhibited in a time- and concentration-dependent manner by alpha-tcp. The IC50 of alpha-tcp on an IL-1-induced response was 45 microM. The inhibition correlated with a decrease in steady state levels of E-selectin mRNA and cell surface expression of E-selectin which is consistent with the ability of a monoclonal antibody to E-selectin to inhibit monocytic cell adhesion in this system. Probucol (50 microM) and N-acetylcysteine (20 mM) also inhibited agonist-induced monocytic cell adhesion; whereas, several other antioxidants had no significant effect. Protein kinase C (PKC) does not appear to play a role in the alpha-tcp effect since no suppression of phosphorylation of PKC substrates was observed. Activation of the transcription factor NF-kappa B is reported to be necessary but not sufficient for E-selectin expression in EC. Electrophoretic mobility shift assays failed to show an alpha-tcp-induced decrease in activation of this transcription factor after cytokine stimulation. It has been hypothesized that alpha-tcp acts as an anti-atherosclerotic molecule by inhibiting generation of oxidized LDL--a putative triggering molecule in the atherosclerotic process. Our results point to a novel alternative mechanism of action of alpha-tcp.

Full text

PDF
592

Images in this article

596Image
on p.596
596Image
on p.596
596Image
on p.596
597Image
on p.597
598Image
on p.598

Selected References

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

  1. Barber A. A. Lipid peroxidation in rat tissue homogenates: Interaction of iron and ascorbic acid as the normal catalytic mechanism. Lipids. 1966 Mar;1(2):146–151. doi: 10.1007/BF02533008. [DOI] [PubMed] [Google Scholar]
  2. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  4. Bhat N. R. Phosphorylation of MARCKS (80-kDa) protein, a major substrate for protein kinase C in oligodendroglial progenitors. J Neurosci Res. 1991 Oct;30(2):447–454. doi: 10.1002/jnr.490300222. [DOI] [PubMed] [Google Scholar]
  5. Biemond P., Swaak A. J., van Eijk H. G., Koster J. F. Superoxide dependent iron release from ferritin in inflammatory diseases. Free Radic Biol Med. 1988;4(3):185–198. doi: 10.1016/0891-5849(88)90026-3. [DOI] [PubMed] [Google Scholar]
  6. Blackshear P. J., Wen L., Glynn B. P., Witters L. A. Protein kinase C-stimulated phosphorylation in vitro of a Mr 80,000 protein phosphorylated in response to phorbol esters and growth factors in intact fibroblasts. Distinction from protein kinase C and prominence in brain. J Biol Chem. 1986 Jan 25;261(3):1459–1469. [PubMed] [Google Scholar]
  7. Blank V., Kourilsky P., Israël A. NF-kappa B and related proteins: Rel/dorsal homologies meet ankyrin-like repeats. Trends Biochem Sci. 1992 Apr;17(4):135–140. doi: 10.1016/0968-0004(92)90321-y. [DOI] [PubMed] [Google Scholar]
  8. Boscoboinik D., Szewczyk A., Hensey C., Azzi A. Inhibition of cell proliferation by alpha-tocopherol. Role of protein kinase C. J Biol Chem. 1991 Apr 5;266(10):6188–6194. [PubMed] [Google Scholar]
  9. Burton G. W., Ingold K. U. Vitamin E as an in vitro and in vivo antioxidant. Ann N Y Acad Sci. 1989;570:7–22. doi: 10.1111/j.1749-6632.1989.tb14904.x. [DOI] [PubMed] [Google Scholar]
  10. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  11. Carlos T., Kovach N., Schwartz B., Rosa M., Newman B., Wayner E., Benjamin C., Osborn L., Lobb R., Harlan J. Human monocytes bind to two cytokine-induced adhesive ligands on cultured human endothelial cells: endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1. Blood. 1991 May 15;77(10):2266–2271. [PubMed] [Google Scholar]
  12. Chan A. C., Tran K. The uptake of (R,R,R)alpha-tocopherol by human endothelial cells in culture. Lipids. 1990 Jan;25(1):17–21. doi: 10.1007/BF02562422. [DOI] [PubMed] [Google Scholar]
  13. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  14. Chow C. K. Vitamin E and oxidative stress. Free Radic Biol Med. 1991;11(2):215–232. doi: 10.1016/0891-5849(91)90174-2. [DOI] [PubMed] [Google Scholar]
  15. Collins T., Williams A., Johnston G. I., Kim J., Eddy R., Shows T., Gimbrone M. A., Jr, Bevilacqua M. P. Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1. J Biol Chem. 1991 Feb 5;266(4):2466–2473. [PubMed] [Google Scholar]
  16. Corwin L. M., Gordon R. K. Vitamin E and immune regulation. Ann N Y Acad Sci. 1982;393:437–451. doi: 10.1111/j.1749-6632.1982.tb31282.x. [DOI] [PubMed] [Google Scholar]
  17. Cotran R. S. American Association of Pathologists president's address. New roles for the endothelium in inflammation and immunity. Am J Pathol. 1987 Dec;129(3):407–413. [PMC free article] [PubMed] [Google Scholar]
  18. Crawford D. W., Blankenhorn D. H. Arterial wall oxygenation, oxyradicals, and atherosclerosis. Atherosclerosis. 1991 Aug;89(2-3):97–108. doi: 10.1016/0021-9150(91)90049-9. [DOI] [PubMed] [Google Scholar]
  19. Datta S., Soong C. J., Wang D. M., Harter M. L. A purified adenovirus 289-amino-acid E1A protein activates RNA polymerase III transcription in vitro and alters transcription factor TFIIIC. J Virol. 1991 Oct;65(10):5297–5304. doi: 10.1128/jvi.65.10.5297-5304.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. DiCorleto P. E., Chisolm G. M., 3rd Participation of the endothelium in the development of the atherosclerotic plaque. Prog Lipid Res. 1986;25(1-4):365–374. doi: 10.1016/0163-7827(86)90074-3. [DOI] [PubMed] [Google Scholar]
  21. DiCorleto P. E., de la Motte C. A. Characterization of the adhesion of the human monocytic cell line U937 to cultured endothelial cells. J Clin Invest. 1985 Apr;75(4):1153–1161. doi: 10.1172/JCI111810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. DiCorleto P. E., de la Motte C. A. Role of cell surface carbohydrate moieties in monocytic cell adhesion to endothelium in vitro. J Immunol. 1989 Dec 1;143(11):3666–3672. [PubMed] [Google Scholar]
  23. DiCorleto P. E., de la Motte C. A. Thrombin causes increased monocytic-cell adhesion to endothelial cells through a protein kinase C-dependent pathway. Biochem J. 1989 Nov 15;264(1):71–77. doi: 10.1042/bj2640071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Esterbauer H., Striegl G., Puhl H., Oberreither S., Rotheneder M., el-Saadani M., Jürgens G. The role of vitamin E and carotenoids in preventing oxidation of low density lipoproteins. Ann N Y Acad Sci. 1989;570:254–267. doi: 10.1111/j.1749-6632.1989.tb14925.x. [DOI] [PubMed] [Google Scholar]
  26. Faggiotto A., Ross R., Harker L. Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. Arteriosclerosis. 1984 Jul-Aug;4(4):323–340. doi: 10.1161/01.atv.4.4.323. [DOI] [PubMed] [Google Scholar]
  27. Fajardo L. F. The complexity of endothelial cells. A review. Am J Clin Pathol. 1989 Aug;92(2):241–250. doi: 10.1093/ajcp/92.2.241. [DOI] [PubMed] [Google Scholar]
  28. Farago A., Nishizuka Y. Protein kinase C in transmembrane signalling. FEBS Lett. 1990 Aug 1;268(2):350–354. doi: 10.1016/0014-5793(90)81284-u. [DOI] [PubMed] [Google Scholar]
  29. Farber J. L., Kyle M. E., Coleman J. B. Mechanisms of cell injury by activated oxygen species. Lab Invest. 1990 Jun;62(6):670–679. [PubMed] [Google Scholar]
  30. Faruqi R. M., DiCorleto P. E. Mechanisms of monocyte recruitment and accumulation. Br Heart J. 1993 Jan;69(1 Suppl):S19–S29. doi: 10.1136/hrt.69.1_suppl.s19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Fox P. L., DiCorleto P. E. Regulation of production of a platelet-derived growth factor-like protein by cultured bovine aortic endothelial cells. J Cell Physiol. 1984 Nov;121(2):298–308. doi: 10.1002/jcp.1041210206. [DOI] [PubMed] [Google Scholar]
  32. Frei B., England L., Ames B. N. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6377–6381. doi: 10.1073/pnas.86.16.6377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Gerrity R. G., Naito H. K., Richardson M., Schwartz C. J. Dietary induced atherogenesis in swine. Morphology of the intima in prelesion stages. Am J Pathol. 1979 Jun;95(3):775–792. [PMC free article] [PubMed] [Google Scholar]
  34. Gerrity R. G. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol. 1981 May;103(2):181–190. [PMC free article] [PubMed] [Google Scholar]
  35. Graber N., Gopal T. V., Wilson D., Beall L. D., Polte T., Newman W. T cells bind to cytokine-activated endothelial cells via a novel, inducible sialoglycoprotein and endothelial leukocyte adhesion molecule-1. J Immunol. 1990 Aug 1;145(3):819–830. [PubMed] [Google Scholar]
  36. Hartwig J. H., Thelen M., Rosen A., Janmey P. A., Nairn A. C., Aderem A. MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin. Nature. 1992 Apr 16;356(6370):618–622. doi: 10.1038/356618a0. [DOI] [PubMed] [Google Scholar]
  37. Jaffe E. A. Cell biology of endothelial cells. Hum Pathol. 1987 Mar;18(3):234–239. doi: 10.1016/s0046-8177(87)80005-9. [DOI] [PubMed] [Google Scholar]
  38. Janero D. R. Therapeutic potential of vitamin E in the pathogenesis of spontaneous atherosclerosis. Free Radic Biol Med. 1991;11(1):129–144. doi: 10.1016/0891-5849(91)90193-7. [DOI] [PubMed] [Google Scholar]
  39. Jialal I., Grundy S. M. Preservation of the endogenous antioxidants in low density lipoprotein by ascorbate but not probucol during oxidative modification. J Clin Invest. 1991 Feb;87(2):597–601. doi: 10.1172/JCI115035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Joris I., Zand T., Nunnari J. J., Krolikowski F. J., Majno G. Studies on the pathogenesis of atherosclerosis. I. Adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats. Am J Pathol. 1983 Dec;113(3):341–358. [PMC free article] [PubMed] [Google Scholar]
  41. Kagan V. E. Tocopherol stabilizes membrane against phospholipase A, free fatty acids, and lysophospholipids. Ann N Y Acad Sci. 1989;570:121–135. doi: 10.1111/j.1749-6632.1989.tb14913.x. [DOI] [PubMed] [Google Scholar]
  42. Kaneko T., Nakano S., Matsuo M. Protective effect of vitamin E on linoleic acid hydroperoxide-induced injury to human endothelial cells. Lipids. 1991 May;26(5):345–348. doi: 10.1007/BF02537196. [DOI] [PubMed] [Google Scholar]
  43. Klebanoff S. J., Vadas M. A., Harlan J. M., Sparks L. H., Gamble J. R., Agosti J. M., Waltersdorph A. M. Stimulation of neutrophils by tumor necrosis factor. J Immunol. 1986 Jun 1;136(11):4220–4225. [PubMed] [Google Scholar]
  44. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  45. Lane T. A., Lamkin G. E., Wancewicz E. V. Protein kinase C inhibitors block the enhanced expression of intercellular adhesion molecule-1 on endothelial cells activated by interleukin-1, lipopolysaccharide and tumor necrosis factor. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1273–1281. doi: 10.1016/0006-291x(90)91587-i. [DOI] [PubMed] [Google Scholar]
  46. Laudicina D. C., Marnett L. J. Enhancement of hydroperoxide-dependent lipid peroxidation in rat liver microsomes by ascorbic acid. Arch Biochem Biophys. 1990 Apr;278(1):73–80. doi: 10.1016/0003-9861(90)90233-o. [DOI] [PubMed] [Google Scholar]
  47. Leeuwenberg J. F., Jeunhomme T. M., Buurman W. A. Role of ELAM-1 in adhesion of monocytes to activated human endothelial cells. Scand J Immunol. 1992 Mar;35(3):335–341. doi: 10.1111/j.1365-3083.1992.tb02866.x. [DOI] [PubMed] [Google Scholar]
  48. Levin E. G., Santell L. Phosphorylation of an Mr = 29,000 protein by IL-1 is susceptible to partial down-regulation after endothelial cell activation. J Immunol. 1991 Jun 1;146(11):3772–3778. [PubMed] [Google Scholar]
  49. Levin E. G., Santell L. Thrombin- and histamine-induced signal transduction in human endothelial cells. Stimulation and agonist-dependent desensitization of protein phosphorylation. J Biol Chem. 1991 Jan 5;266(1):174–181. [PubMed] [Google Scholar]
  50. Lewis L. J., Hoak J. C., Maca R. D., Fry G. L. Replication of human endothelial cells in culture. Science. 1973 Aug 3;181(4098):453–454. doi: 10.1126/science.181.4098.453. [DOI] [PubMed] [Google Scholar]
  51. Mahoney C. W., Azzi A. Vitamin E inhibits protein kinase C activity. Biochem Biophys Res Commun. 1988 Jul 29;154(2):694–697. doi: 10.1016/0006-291x(88)90195-7. [DOI] [PubMed] [Google Scholar]
  52. Marui N., Offermann M. K., Swerlick R., Kunsch C., Rosen C. A., Ahmad M., Alexander R. W., Medford R. M. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells. J Clin Invest. 1993 Oct;92(4):1866–1874. doi: 10.1172/JCI116778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Matsubara T., Ziff M. Superoxide anion release by human endothelial cells: synergism between a phorbol ester and a calcium ionophore. J Cell Physiol. 1986 May;127(2):207–210. doi: 10.1002/jcp.1041270203. [DOI] [PubMed] [Google Scholar]
  54. Meier B., Radeke H. H., Selle S., Younes M., Sies H., Resch K., Habermehl G. G. Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha. Biochem J. 1989 Oct 15;263(2):539–545. doi: 10.1042/bj2630539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Montgomery K. F., Osborn L., Hession C., Tizard R., Goff D., Vassallo C., Tarr P. I., Bomsztyk K., Lobb R., Harlan J. M. Activation of endothelial-leukocyte adhesion molecule 1 (ELAM-1) gene transcription. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6523–6527. doi: 10.1073/pnas.88.15.6523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Myers C. L., Desai S. N., Schembri-King J., Letts G. L., Wallace R. W. Discriminatory effects of protein kinase inhibitors and calcium ionophore on endothelial ICAM-1 induction. Am J Physiol. 1992 Feb;262(2 Pt 1):C365–C373. doi: 10.1152/ajpcell.1992.262.2.C365. [DOI] [PubMed] [Google Scholar]
  57. Nishizuka Y. The Albert Lasker Medical Awards. The family of protein kinase C for signal transduction. JAMA. 1989 Oct 6;262(13):1826–1833. [PubMed] [Google Scholar]
  58. Nègre-Salvayre A., Affany A., Hariton C., Salvayre R. Additional antilipoperoxidant activities of alpha-tocopherol and ascorbic acid on membrane-like systems are potentiated by rutin. Pharmacology. 1991;42(5):262–272. doi: 10.1159/000138807. [DOI] [PubMed] [Google Scholar]
  59. Packer L., Landvik S. Vitamin E: introduction to biochemistry and health benefits. Ann N Y Acad Sci. 1989;570:1–6. doi: 10.1111/j.1749-6632.1989.tb14903.x. [DOI] [PubMed] [Google Scholar]
  60. Recalde H. R. A simple method of obtaining monocytes in suspension. J Immunol Methods. 1984 Apr 13;69(1):71–77. doi: 10.1016/0022-1759(84)90278-3. [DOI] [PubMed] [Google Scholar]
  61. Renkonen R., Mennander A., Ustinov J., Mattila P. Activation of protein kinase C is crucial in the regulation of ICAM-1 expression on endothelial cells by interferon-gamma. Int Immunol. 1990;2(8):719–724. doi: 10.1093/intimm/2.8.719. [DOI] [PubMed] [Google Scholar]
  62. Rimm E. B., Stampfer M. J., Ascherio A., Giovannucci E., Colditz G. A., Willett W. C. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993 May 20;328(20):1450–1456. doi: 10.1056/NEJM199305203282004. [DOI] [PubMed] [Google Scholar]
  63. Ritchie A. J., Johnson D. R., Ewenstein B. M., Pober J. S. Tumor necrosis factor induction of endothelial cell surface antigens is independent of protein kinase C activation or inactivation. Studies with phorbol myristate acetate and staurosporine. J Immunol. 1991 May 1;146(9):3056–3062. [PubMed] [Google Scholar]
  64. Rosen G. M., Freeman B. A. Detection of superoxide generated by endothelial cells. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7269–7273. doi: 10.1073/pnas.81.23.7269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
  66. Rozengurt E., Rodriguez-Pena M., Smith K. A. Phorbol esters, phospholipase C, and growth factors rapidly stimulate the phosphorylation of a Mr 80,000 protein in intact quiescent 3T3 cells. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7244–7248. doi: 10.1073/pnas.80.23.7244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Sadrzadeh S. M., Eaton J. W. Hemoglobin-mediated oxidant damage to the central nervous system requires endogenous ascorbate. J Clin Invest. 1988 Nov;82(5):1510–1515. doi: 10.1172/JCI113759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Santell L., Bartfeld N. S., Levin E. G. Identification of a protein transiently phosphorylated by activators of endothelial cell function as the heat-shock protein HSP27. A possible role for protein kinase C. Biochem J. 1992 Jun 15;284(Pt 3):705–710. doi: 10.1042/bj2840705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Schreck R., Baeuerle P. A. A role for oxygen radicals as second messengers. Trends Cell Biol. 1991 Aug;1(2-3):39–42. doi: 10.1016/0962-8924(91)90072-h. [DOI] [PubMed] [Google Scholar]
  70. Schreck R., Meier B., Männel D. N., Dröge W., Baeuerle P. A. Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. J Exp Med. 1992 May 1;175(5):1181–1194. doi: 10.1084/jem.175.5.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Schreck R., Rieber P., Baeuerle P. A. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J. 1991 Aug;10(8):2247–2258. doi: 10.1002/j.1460-2075.1991.tb07761.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Schwartz C. J., Sprague E. A., Kelley J. L., Valente A. J., Suenram C. A. Aortic intimal monocyte recruitment in the normo and hypercholesterolemic baboon (Papio cynocephalus). An ultrastructural study: implications in atherogenesis. Virchows Arch A Pathol Anat Histopathol. 1985;405(2):175–191. doi: 10.1007/BF00704370. [DOI] [PubMed] [Google Scholar]
  73. Shankar R., de la Motte C. A., DiCorleto P. E. 3-Deazaadenosine inhibits thrombin-stimulated platelet-derived growth factor production and endothelial-leukocyte adhesion molecule-1-mediated monocytic cell adhesion in human aortic endothelial cells. J Biol Chem. 1992 May 5;267(13):9376–9382. [PubMed] [Google Scholar]
  74. Stabel S., Parker P. J. Protein kinase C. Pharmacol Ther. 1991;51(1):71–95. doi: 10.1016/0163-7258(91)90042-k. [DOI] [PubMed] [Google Scholar]
  75. Stampfer M. J., Hennekens C. H., Manson J. E., Colditz G. A., Rosner B., Willett W. C. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993 May 20;328(20):1444–1449. doi: 10.1056/NEJM199305203282003. [DOI] [PubMed] [Google Scholar]
  76. Steinberg D. Antioxidants in the prevention of human atherosclerosis. Summary of the proceedings of a National Heart, Lung, and Blood Institute Workshop: September 5-6, 1991, Bethesda, Maryland. Circulation. 1992 Jun;85(6):2337–2344. doi: 10.1161/01.cir.85.6.2337. [DOI] [PubMed] [Google Scholar]
  77. Stähelin H. B., Gey K. F., Eichholzer M., Lüdin E., Brubacher G. Cancer mortality and vitamin E status. Ann N Y Acad Sci. 1989;570:391–399. doi: 10.1111/j.1749-6632.1989.tb14938.x. [DOI] [PubMed] [Google Scholar]
  78. Taylor R. G., Lewis J. C. Endothelial cell proliferation and monocyte adhesion to atherosclerotic lesions of white carneau pigeons. Am J Pathol. 1986 Oct;125(1):152–160. [PMC free article] [PubMed] [Google Scholar]
  79. Tengerdy R. P. Vitamin E, immune response, and disease resistance. Ann N Y Acad Sci. 1989;570:335–344. doi: 10.1111/j.1749-6632.1989.tb14932.x. [DOI] [PubMed] [Google Scholar]
  80. Thornton S. C., Mueller S. N., Levine E. M. Human endothelial cells: use of heparin in cloning and long-term serial cultivation. Science. 1983 Nov 11;222(4624):623–625. doi: 10.1126/science.6635659. [DOI] [PubMed] [Google Scholar]
  81. Whelan J., Ghersa P., Hooft van Huijsduijnen R., Gray J., Chandra G., Talabot F., DeLamarter J. F. An NF kappa B-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule 1 (ELAM-1) gene transcription. Nucleic Acids Res. 1991 May 25;19(10):2645–2653. doi: 10.1093/nar/19.10.2645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Wills E. D. Mechanisms of lipid peroxide formation in animal tissues. Biochem J. 1966 Jun;99(3):667–676. doi: 10.1042/bj0990667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Wolfman A., Macara I. G. Elevated levels of diacylglycerol and decreased phorbol ester sensitivity in ras-transformed fibroblasts. Nature. 1987 Jan 22;325(6102):359–361. doi: 10.1038/325359a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES