Skip to main content
SpringerLink
Log in

Human Studies of Antioxidants and Vascular Function

  • Chapter
Oxidative Stress and Vascular Disease

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 224))

  • 403 Accesses

Abstract

Antioxidants are commonly consumed by patients for the prevention and treatment of cardiovascular disease (CVD) based upon recent clinical studies that suggest an association between increased intake of certain antioxidant vitamins and reduced risk for CVD. It is important to realize, however, that the putative mechanisms of any benefit remain uncertain. Investigations in animal models indicate that increased oxidative stress contributes to the atherogenic process and to the development of vascular dysfunction. In such models, antioxidant treatment has often been shown to limit the extent of atherosclerosis and maintain normal vascular function. If applicable to humans, these effects could explain the clinical benefits of antioxidants.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Quinn MT, Parthasarathy S, Fong LG, Steinberg D. Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci USA. 1987;84:2995.

    Article  PubMed  CAS  Google Scholar 

  2. Diaz MN, Frei B, Vita JA, Keaney JF Jr. Antioxidants and atherosclerotic heart disease. N Engl J Med. 1997;337:408.

    Article  PubMed  CAS  Google Scholar 

  3. Walldius G, Erikson U, Olsson AG, Bergstrand L, Hadell K, Johansson J, Kaijser L, Lassvik C, Molgaard J, Nilsson S. The effect of probucol on femoral atherosclerosis: the Probucol Quantitative Regression Swedish Trial (PQRST). Am J Cardiol. 1994;74:875.

    Article  PubMed  CAS  Google Scholar 

  4. Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996;347:781.

    Article  PubMed  CAS  Google Scholar 

  5. Levine GN, Keaney JF Jr, Vita JA. Cholesterol reduction in cardiovascular disease: Clinical benefits and possible mechanisms. N Engl J Med. 1995;332:512.

    Article  PubMed  CAS  Google Scholar 

  6. Libby P. Molecular basis of the acute coronary syndromes. Circulation. 1995;91:2844.

    Article  PubMed  CAS  Google Scholar 

  7. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes (Part 1). N Engl J Med. 1992;326:242.

    Article  PubMed  CAS  Google Scholar 

  8. Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988;333:664.

    Article  PubMed  CAS  Google Scholar 

  9. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA. 1987;84:9265.

    Article  PubMed  CAS  Google Scholar 

  10. Young MA, Vatner SF. Regulation of large coronary arteries. Circ Res. 1986;59:579.

    Article  PubMed  CAS  Google Scholar 

  11. Shimokawa H, Aarhus L, Vanhoutte PM. Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin. Circ Res. 1987;61:256.

    Article  PubMed  CAS  Google Scholar 

  12. Furchgott R. Role of endothelium in responses of vascular smooth muscle. Circ Res. 1983;53:557.

    Article  PubMed  CAS  Google Scholar 

  13. Oates JA, Fitzgerald GA, Branch RA, Jackson EK, Knapp HR, Roberts LJ 2d. Clinical implications of Prostaglandin and thromboxane A2 formation. N Engl J Med. 1988;319:689.

    Article  PubMed  CAS  Google Scholar 

  14. Chen G, Suzuki H, Weston AH. Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels. Br J Pharmacol. 1988;95:1165.

    Article  PubMed  CAS  Google Scholar 

  15. Pearson JD, Gordon JL. Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides. Nature. 1979;281:384.

    Article  PubMed  CAS  Google Scholar 

  16. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:411.

    Article  PubMed  CAS  Google Scholar 

  17. Radomski MW, Palmer RM, Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol. 1987;92:181.

    Article  PubMed  CAS  Google Scholar 

  18. Marcum JA, Rosenberg RD: Heparin-like molecules with anticoagulant activity are synthesized by cultured endothelial cells. Biochem Biophys Res Commun. 1985; 126:365.

    Article  PubMed  CAS  Google Scholar 

  19. Esmon NL, Owen WG, Esmon CT. Isolation of a membrane bound cofactor for thrombincatalyzed activation of protein C. J Biol Chem. 1982;257:859.

    PubMed  CAS  Google Scholar 

  20. Loskutoff D, Edgington T. Synthesis of a fibrinolytic activator and inhibitor by endothelial cells. Proc Natl Acad Sci USA. 1977;74:3903.

    Article  PubMed  CAS  Google Scholar 

  21. Berk BC, Alexander RW. Commentary: Vasoactive effects of growth factors. Biochem Pharmacol. 1989;38:219.

    Article  PubMed  CAS  Google Scholar 

  22. Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med. 1994;330:1431.

    Article  PubMed  CAS  Google Scholar 

  23. Gokce N, Keaney JF Jr, Vita JA Endotheliopathies: Clinical manifestations of endothelial dysfunction, in Loscalzo J, Shafer AI (eds): Thrombosis and Hemorrhage, Second ed., Williams and Wilkins, 1998, pp. 901–924.

    Google Scholar 

  24. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells, J Clin Invest. 1989;83:1774.

    Article  PubMed  CAS  Google Scholar 

  25. Cooke JP, Singer AH, Tsao P, Zera P, Rowan RA, Dillingham ME. Antiatherogenic effects of L-arginine in hypercholesterolemic rabbits. J Clin Invest. 1992;90:1168.

    Article  PubMed  CAS  Google Scholar 

  26. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med.1986;315:1046.

    Article  PubMed  CAS  Google Scholar 

  27. Bossaller C, Habib GB, Yamamoto H, Williams C, Wells S, Henry PD. Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5’-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest. 1987;79:170.

    Article  PubMed  CAS  Google Scholar 

  28. Vita JA, Treasure CB, Nabel EG, McLenachan JM, Fish RD, Yeung AC, Vekshtein VI, Selwyn AP, Ganz P. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation. 1990;81:491.

    Article  PubMed  CAS  Google Scholar 

  29. Johnstone MT, Creager SJ, Scales KM, Cusco JA, Lee BK, Creager MA. Impaired endotheliumdependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation. 1993;88:2510.

    Article  PubMed  CAS  Google Scholar 

  30. Creager MA, Cooke JP, Mendelsohn ME, Gallagher SJ, Coleman SM, Loscalzo J, Dzau VJ. Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest. 1990;86:228.

    Article  PubMed  CAS  Google Scholar 

  31. Panza JA, Quyyumi AA, Brush JE, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990;323:22.

    Article  PubMed  CAS  Google Scholar 

  32. Elliot TG, Barth JD, Mancini GBJ. Effects of Vitamin E on Endothelial Function in Men After Myocardial Infarction. Am J Cardiol. 1995;76:1188.

    Article  Google Scholar 

  33. Vita JA, Keaney JF Jr. Ultrasound assessment of endothelial vasomotor function, in Lanzer P, Lipton M (eds): Diagnostics of vascular diseases: Principals and technology, Second ed. Berlin, Springer, 1996, pp. 249–259.

    Google Scholar 

  34. Lieberman EH, Gerhard MD, Uehata A, Selwyn AP, Ganz P, Yeung AC, Creager MA. Flowinduced vasodilation of the human brachial artery is impaired in patients <40 years of age with coronary artery disease. Am J Cardiol. 1996;78:1210.

    Article  PubMed  CAS  Google Scholar 

  35. Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Luscher TF. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation. 1995;91:1314.

    CAS  Google Scholar 

  36. Lieberman EH, Uehata A, Polak J, Ganz P, Selwyn AP, Creager MA, Yeung AC. Flow-mediated vasodilation is impaired in the brachial artery of patients with coronary disease or diabetes mellitus (abst). Clin Res. 1993;41:217A.

    Google Scholar 

  37. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Leiberman E, Ganz P, Creager MA, Yeung AC, Selwyn AP. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26:1235.

    Article  PubMed  CAS  Google Scholar 

  38. Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type Plasminogen activator and risk of myocardial infarction. Lancet. 1993;341:1165.

    Article  PubMed  CAS  Google Scholar 

  39. Collins T. Endothelial Nuclear Factor-DB and the Initiation of the Atherosclerotic Lesion. Lab Invest. 1993;68:499.

    PubMed  CAS  Google Scholar 

  40. Ridker PM, Hennekens CH, Roitman-Johnson B, Allen J. Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet. 1998;351:88.

    Article  PubMed  CAS  Google Scholar 

  41. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336, No. 14:973.

    Article  PubMed  CAS  Google Scholar 

  42. Gordon JB, Ganz P, Nabel EG, Fish RD, Zebede J, Mudge GH, Alexander RW, Selwyn AP. Atherosclerosis influences the vasomotor response of epicardial coronary arteries to exercise. J Clin Invest. 1989;83:1946.

    Article  PubMed  CAS  Google Scholar 

  43. Yeung AC, Vekshtein VI, Krantz DS, Vita JA, Ryan TJ Jr, Ganz P, Selwyn AP. The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med. 1991;325:1551.

    Article  PubMed  CAS  Google Scholar 

  44. Bogaty P, Hackett D, Davies G, Maseri A. Vasoreactivity of the culprit lesion in unstable angina. Circulation. 1994;90:5.

    Article  PubMed  CAS  Google Scholar 

  45. Okumura K, Yasue H, Matsuyama K, Ogawa H, Morikami Y, Obata K, Sakaino N. Effect of acetylcholine on the highly stenotic coronary artery: difference between the constrictor response of the infarct-related coronary artery and that of the noninfarct-related artery. J Am Coll Cardiol. 1992;19:752.

    Article  PubMed  CAS  Google Scholar 

  46. Gryglewski RJ, Palmer RM, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature. 1986;320:454.

    Article  PubMed  CAS  Google Scholar 

  47. Mugge A, Elwell JK, Peterson TE, Harrison DG. Release of intact endothelium-derived relaxing factor depends on endothelial Superoxide dismutase activity. Am J Physiol. [Cell Physiol. 29] 1991;260:C219.

    PubMed  CAS  Google Scholar 

  48. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial Superoxide anion production. J Clin Invest. 1993;91:2546.

    Article  PubMed  CAS  Google Scholar 

  49. Mugge A, Elwell JH, Peterson TE, Hofmeyer TG, Heistad DD, Harrison DG. Chronic treatment with polyethylene-glycolated Superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits. Circ Res. 1991;69:1293.

    Article  PubMed  CAS  Google Scholar 

  50. Morel DW, Hessler GM, Chisolm GM. Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid. J Lipid Res. 1983;24:1070.

    PubMed  CAS  Google Scholar 

  51. Chin JH, Aznar S, Hoffman BB. Inactivation of endothelium-derived relaxing factor by oxidized lipoproteins. J Clin Invest. 1992;89:10.

    Article  PubMed  CAS  Google Scholar 

  52. Kugiyama K, Kerns SA, Morrisett JD, Roberts R, Henry PD. Impairment of endotheliumdependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Nature. 1990;344:160.

    Article  PubMed  CAS  Google Scholar 

  53. Liao JK, Shin WS, Lee WY, Clark SL. Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase. J Biol Chem. 1995;270:319.

    Article  PubMed  CAS  Google Scholar 

  54. Boulanger CM, Tanner FC, Bea ML, Hahn AW, Werner A, Luscher TF. Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium. Circ Res. 1992;70:1191.

    Article  PubMed  CAS  Google Scholar 

  55. Weis JR, Pitas RE, Wilson BD, Rodgers GM. Oxidized low-density lipoprotein increases cultured human endothelial cell tissue factor activity and reduces protein C activation. FASEB J. 1991;5:2459.

    PubMed  CAS  Google Scholar 

  56. Kume N, Cybulsky MI, Gimbrone MA Jr. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest. 1992;90:1138.

    Article  PubMed  CAS  Google Scholar 

  57. Kugiyama K, Sakamoto T, Misumi I, Sugiyama S, Ohgushi M, Ogawa H, Horiguchi M, Yasue H. Transferable lipids in oxidized low-density lipoprotein stimulate Plasminogen activator inhibitor-1 and inhibit tissue-type Plasminogen activator release from endothelial cells. Circ Res. 1993;73:335.

    Article  PubMed  CAS  Google Scholar 

  58. Ohara Y, Peterson TE, Zheng B, Kuo JF, Harrison DG. Lysophosphatidylcholine increases vascular Superoxide anion production via protein kinase C activation. Arterioscler Thromb. 1994;14:1007.

    Article  PubMed  CAS  Google Scholar 

  59. Heitzer T, Yla-Herttuala S, Luoma J, Kurz S, Munzel T, Just H, Olschewski M, Drexler H. Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia. Role of oxidized LDL. Circulation. 1996;93:1346.

    Article  PubMed  CAS  Google Scholar 

  60. Briviba K, Sies H. Nonenzymatic antioxidant defense systems, in Frei B (ed): Natural antioxidants in human health and disease. San Diego, Academic Press, 1994, pp. 107–128.

    Google Scholar 

  61. Reaven PD, Khouw A, Beltz WF, Parthasarathy S, Witztum JL. Effect of dietary antioxidant combinations in humans, protection of LDL by vitamin E but not beta carotene. Arterioscler Thromb. 1993;13:590.

    Article  PubMed  CAS  Google Scholar 

  62. Gaziano JM, Manson JE, Hennekens CH. Natural antioxidants and cardiovascular disease: Observational epidemiologic studies and randomized trials, in Frei B (ed): Natural antioxidants in human health and disease. San Diego, CA, Academic Press, Inc., 1994, pp. 387–409.

    Google Scholar 

  63. Rapola JM, Virtamo J, Ripatti S, Huttunen JK, Albanes D, Taylor PR, Heionen OP. Randomised trial of a-tocopherol and B-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet. 1997;349:1715.

    Article  PubMed  CAS  Google Scholar 

  64. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993;328:1444.

    Article  PubMed  CAS  Google Scholar 

  65. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993;328:1450.

    Article  PubMed  CAS  Google Scholar 

  66. Tornwall ME, Virtamo J, Haukka JK, Aro A, Albanes D, Edwards BK, Huttunen JK: Effect of atocopherol (vitamin E) and b-carotene supplementation on the incidence of intermittent claudication in male smokers. Arterioscler Thromb Vasc Biol. 1997; 17:3475.

    Article  PubMed  CAS  Google Scholar 

  67. Williams HTG, Fenna D, MacBeth RA. Alpha Tocopherol in the treatment of intermittent claudication. Surg Gyn Obstetrics. 1971;48:662.

    Google Scholar 

  68. Haeger K. Long-time treatment of intermittent claudication with vitamin E. Am J Clin Nutr. 1974;27:1179.

    PubMed  CAS  Google Scholar 

  69. Kritchevsky SB, Shimakawa T, Tell GS, Dennis B, Carpenter M, Eckfeldt JH, Peacher-Ryan H, Heiss G. Dietary antioxidants and carotid artery wall thickness: The ARJC study. Circulation. 1995;92:2142.

    Article  PubMed  CAS  Google Scholar 

  70. Hodis HN, Mack WJ, LaBree L, Cashin-Hemphill L, Sevanian A, Johnson R, Azen SP. Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis. JAMA 1995;273:1849.

    Article  PubMed  CAS  Google Scholar 

  71. Lynch SM, Frei B. Antioxidants as antiatherogens: Animal studies, in Frei B (ed): Natural antioxidants in human health and disease. San Diego, CA, Academic Press, 1994, pp. 353–386.

    Google Scholar 

  72. Loscalzo J. Regression of coronary atherosclerosis. N Engl J Med. 1990;323:1337.

    Article  PubMed  CAS  Google Scholar 

  73. Keaney JF Jr, Gaziano JM, Xu A, Frei B, Curran-Celantano J, Shwaery GT, Loscalzo J, Vita JA. Dietary antioxidants preserve endothelium-dependent vessel relaxation in cholesterol-fed rabbits. Proc Natl Acad Sci USA. 1993;90:11880.

    Article  PubMed  CAS  Google Scholar 

  74. Andersson TLG, Matz J, Ferns GAA, Anggard EE. Vitamin E reverses cholesterol-induced endothelial dysfunction in the rabbit coronary circulation. Atherosclerosis. 1994;111:39.

    Article  PubMed  CAS  Google Scholar 

  75. Steward-Lee AL, Forster LA, Nourooz-Zadeh J, Ferns GAA, Anggard EE. Vitamin E protects against impairment of endothelium-mediated relaxations in cholesterol-fed rabbits. Arterioscler Thromb. 1994;14:494.

    Article  Google Scholar 

  76. Keegan A, Walbank H, Cotter MA, Cameron NE. Chronic vitamin E treatment prevents defective endothelium-dependent relaxation in diabetic rat aorta. Diabetologia. 1995;38:1475.

    Article  PubMed  CAS  Google Scholar 

  77. Faruqi R, De La Motte C, Dicorleto PE. a-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells. J Clin Invest. 1994;94:592.

    Article  PubMed  CAS  Google Scholar 

  78. Devaraj S, Li D, Jialal I. The Effects of Alpha Tocopherol Supplementation on Monocyte Function. J Clin Invest. 1996;98:756.

    Article  PubMed  CAS  Google Scholar 

  79. Gilligan DM, Sack MN, Guetta V, Casino PR, Quyyumi AA, Rader DJ, Panza JA, Cannon RO. Effect of antioxidant vitamins on low density lipoprotein oxidation and impaired endotheliumdependent vasodilation in patients with hypercholesterolemia. J Am Coll Cardiol. 1994;24:1611.

    Article  PubMed  CAS  Google Scholar 

  80. Chowienczyk PJ, Kneale BJ, Brett SE, Paganga G, Jenkins BS, Ritter JM. Lack of effect of vitamin E on L-arginine responsive endothelial dysfunction in patients with mild hypercholesterolemia and coronary artery disease. Clin Sci. 1998;94:129.

    PubMed  CAS  Google Scholar 

  81. McDowell IF, Brennan GM, McEneny J, Young IS, Nicholls DP, McVeigh GE, Bruce I, Trimble ER, Johnston GD. The effect of probucol and vitamin E treatment on the oxidation of lowdensity lipoprotein and forearm vascular responses in humans. Eur J Clin Invest. 1994;24:759.

    Article  PubMed  CAS  Google Scholar 

  82. Neunteufl T, Kostner K, Katzenschlager R, Zehetgruber M, Maurer G. Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men. J Am Coll Cardiol. 1998;32:711.

    Article  PubMed  CAS  Google Scholar 

  83. Motoyama T, Kawano H, Kugiyama K, Hirashima O, Ohgushi M, Tsunoda R, Moriyama Y, Miyao Y, Yoshimura M, Ogawa H, Yasue H. Vitamin E administration improves impairment of endothelium-dependent vasodilation in patients with coronary spastic angina. J Am Coll Cardiol. 1998;32:1672.

    Article  PubMed  CAS  Google Scholar 

  84. Green D, O’Driscoll G, Rankin JM, Maiorana AJ, Taylor RR. Beneficial effect of vitamin E administration on nitric oxide function in subjects with hypercholesterolaemia. Clin Sci. 1998;95:361.

    Article  PubMed  CAS  Google Scholar 

  85. Heitzer T, Yla-Herttuala S, Wild E, Munzel T, Drexler H. Effect of vitamin E on endothelial function and plasma autoantibodies in patients with increased oxidative stress. Circulation. 1997;96:1-417.

    Google Scholar 

  86. Barrett-Connor E, Bush TL. Estrogen and coronary heart disease in women. JAMA. 1991;265:1861.

    Article  PubMed  CAS  Google Scholar 

  87. Stampfer MJ, Colditz GA, Willett WC, Manson JE, Rosner B, Speizer FE, Hennekens CH. Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses’ health study. N Engl J Med. 1991;325:756.

    Article  PubMed  CAS  Google Scholar 

  88. Sullivan JM, Van der Zwaag R, Hughes JP, Madduck V, Kroetz FW, Ramanathan KB, Mirvis DM. Estrogen replacement and coronary artery disease. Effect on survival in post-menopausal women. Arch Intern Med. 1990;150:2557.

    Article  PubMed  CAS  Google Scholar 

  89. Jonas HA, Kronmal RA, Psaty BM, Manolio TA, Meilahn EN, Tell GS, Tracy RP, Robbins JA, Anton-Culver H. Current estrogen-progestin and estrogen replacement therapy in elderly women: association with carotid atherosclerosis. CHS Collaborative Research Group. Cardiovascular Health Study. Ann Epidemiol. 1996;6:314.

    Article  PubMed  CAS  Google Scholar 

  90. Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in women. JAMA. 1998;280:605.

    Article  PubMed  CAS  Google Scholar 

  91. Walsh BW, Schiff I, Rosner B, Greenberg L, Ravnikar V, Sacks FM. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. N Engl J Med. 1991;325:1196.

    Article  PubMed  CAS  Google Scholar 

  92. Bush TL, Barrett-Connor E, Cowan LD, Criqui MH, Wallace RB, Suchindran CM, Tyroler HA, Rifkind BM. Cardiovascular mortality and noncontraceptive use of estrogen in women: results from the Lipid Research Clinics Program Follow-up Study. Circulation. 1987;75:1102.

    Article  PubMed  CAS  Google Scholar 

  93. Mazière C, Auclair M, Ronoveaux MF, Salmon S, Santus R, Mazière JC. Estrogens inhibit copper and cell-mediated modification of low density lipoprotein. Arteriosclerosis. 1991;89:175.

    Article  Google Scholar 

  94. Shwaery GT, Vita JA, Keaney JF Jr. Antioxidant protection of LDL by physiological concentrations of 17-beta estradiol. Circulation. 1997;95:1378.

    Article  PubMed  CAS  Google Scholar 

  95. Sack MN, Rader DJ, Cannon RO 3rd. Oestrogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women. Lancet. 1994;343:269.

    Article  PubMed  CAS  Google Scholar 

  96. Arnal JF, Clamens S, Pechet C, Negre-Salvayre A, Allera C, Girolami JP, Salvayre R, Bayard F. Ethinylestradiol does not enhance the expression of nitric oxide synthase in bovine endothelial cells but increases the release of bioactive nitric oxide by inhibiting Superoxide anion production. Proc Natl Acad Sci USA. 1996;93:4108.

    Article  PubMed  CAS  Google Scholar 

  97. Nègre-Salvayre A, Pieraggi MT, Mabile L, Salvayre R. Protective effect of 17-beta-estradiol against the cytotoxicity of minimally oxidized LDL to cultured bovine aortic endothelial cells. Atherosclerosis. 1992;99:207.

    Article  Google Scholar 

  98. Caulin-Glaser T, Watson CA, Pardi R, Bender JR. Effects of 17-beta-estradiol on cytokineinduced endothelial cell adhesion molecule expression. J Clin Invest. 1996;98:36.

    Article  PubMed  CAS  Google Scholar 

  99. Keaney JF Jr, Shwaery GT, Xu A, Nicolosi RJ, Loscalzo J, Foxall TL, Vita JA. 17-beta-estradiol preserves endothelial vasodilator function and limits LDL oxidation in hypercholesterolemic swine. Circulation. 1994;89:2251.

    Article  PubMed  CAS  Google Scholar 

  100. Lieberman EH, Gerhard MD, Uehata A, Walsh BW, Selwyn AP, Ganz P, Yeung AC, Creager MA. Estrogen improves endothelium-dependent, flow mediated vasodilation in post menopausal women. Ann Intern Med. 1994;121:936.

    PubMed  CAS  Google Scholar 

  101. Gerhard M, Walsh MW, Tawakol A, Haley EA, Creager SJ. Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women. Circulation. 1998;98:1158.

    Article  PubMed  CAS  Google Scholar 

  102. Reis SE, Gloth ST, Blumenthal RS, Resar JR, Zacur HA, Gerstenblith G, Brinker JA. Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. Circulation. 1994;89:52.

    Article  PubMed  CAS  Google Scholar 

  103. Hertog MGL, Feskens EJM, Hollman PCH, Martijn B, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet. 1993;342:1007.

    Article  PubMed  CAS  Google Scholar 

  104. Frankel EN, Kanner J, German JB, Parks E, Kinsella JE. Inhibition of oxidation of human lowdensity lipoprotein by phenolic substances in red wine. Lancet. 1993;341:454.

    Article  PubMed  CAS  Google Scholar 

  105. Korkina LG, Afanas’ev IB. Antioxidant and chelating properties of flavonoids, in Sies H (ed). Antioxidants in disease mechanisms and therapy. San Diego, CA, Academic Press, 1997, pp. 151–163.

    Google Scholar 

  106. Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. Br Med J. 1996;312:478.

    Article  CAS  Google Scholar 

  107. Hertog MGL, Feskens EJM, Kromhout D. Antioxidant flavanols and coronary heart disease risk. Lancet. 1997;349:699.

    Article  PubMed  CAS  Google Scholar 

  108. Rimm EB, Katan MB, Ascherio A, Stampfer MJ, Willett WC. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med. 1996;125:384.

    PubMed  CAS  Google Scholar 

  109. Ishikawa T, Suzukawa M, Ito T, Yoshida H, Ayaori M. Effect of tea flavonoid supplementation on the susceptibility of low-density lipoprotein to oxidative modification. Am J Clin Nutr. 1997;66:261.

    PubMed  CAS  Google Scholar 

  110. van het Hof KH, de Boer HS, Wiseman SA, Lien N, Westrate JA, Tiburg LBM. Consumption of green or black tea does not increase the resistance of LDL to oxidation in humans. Am J Clin Nutr. 1997;66:1125.

    Google Scholar 

  111. Hayek T, Furman B, Vaya JR, Rosenblat M, Belinky P, Coleman R, Elis A, Aviram M: Reduced progression of atherosclerosis in apoplipoprotein E-deficient mice following consumption of red wine or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation. Arterioscler Thromb Vasc Biol. 1997; 17:2744.

    Article  PubMed  CAS  Google Scholar 

  112. Xu R, Yokoyama WH, Irving D, Rein D, Walzern RL, German JB. Effect of dietary catechin and vitamin E on aortic fatty streak accumulation in hypercholesterolemic hamsters. Atherosclerosis. 1998;137:29.

    Article  PubMed  CAS  Google Scholar 

  113. Keaney JF Jr, Frei B. Antioxidant protection of low-density lipoprotein and its role in the prevention of atherosclerotic vascular disease, in Frei B (ed): Natural antioxidants in human health and disease. San Diego, Academic Press, 1994, pp. 303–352.

    Google Scholar 

  114. Carew TE, Schwenke DC, Steinberg D. Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci USA. 1987;84:7725.

    Article  PubMed  CAS  Google Scholar 

  115. Kita T, Nagano Y, Yokode M, Ishii K, Kume N, Ooshima A, Yoshida H, Kawai C. Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia. Proc Natl Acad Sci USA. 1987;84:5928.

    Article  PubMed  CAS  Google Scholar 

  116. Shankar R, Sallis JD, Stanton J, Thomson R: Influence of probucol on early experimental atherogenesis in hypercholesterolemic rats. Atherosclerosis. 1989;78:91.

    Article  PubMed  CAS  Google Scholar 

  117. Johansson J, Olsson AG, Bergstrand L, Elinder LS, Nilsson S, Erikson U, Molgaard J, Holme I, Walldius G. Lowering of HDL2b by probucol partly explains the failure of the drug to affect femoral atherosclerosis in subjects with hypercholesterolemia. A Probucol Quantitative Regression Swedish Trial (PQRST) Report. Arterioscler Thromb Vasc Biol 1995;15:1049.

    Article  PubMed  CAS  Google Scholar 

  118. Tardif JC, Cote G, Lesperance J, Bourassa M, Lambert J, Doucet S, Bilodeau L, Nattel S, de Guise P. Probucol and multivitamins in the prevention of restenosis after coronary angioplasty. N Engl J Med. 1997;337:365.

    Article  PubMed  CAS  Google Scholar 

  119. Sasahara M, Raines E, Chait A, Carew TE, Steinberg D, Wahl PW, Ross R. Inhibition of hypercholesterolemia-induced atherosclerosis in the non-human primate by probucol: I. Is the extent of atherosclerosis related to resistance of LDL to oxidation? J Clin Invest. 1994;94:155.

    Article  PubMed  CAS  Google Scholar 

  120. Simon BC, Haudenschild CC, Cohen RA. Preservation of endothelium-dependent relaxation in atherosclerotic rabbit aorta by probucol. J Cardiovasc Pharmacol. 1993;21:893.

    Article  PubMed  CAS  Google Scholar 

  121. Tesfamariam B, Cohen RA. Free radicals mediate endothelial cell dysfunction caused by elevated glucose. Am J Physiol. 1992;263:H321.

    PubMed  CAS  Google Scholar 

  122. Keaney JF Jr, Xu A, Cunningham DC, Jackson T, Frei B, Vita JA. Dietary probucol preserves endothelial function in cholesterol-fed rabbits by limiting vascular oxidative stress and Superoxide production. J Clin Invest. 1995;95:2520.

    Article  PubMed  CAS  Google Scholar 

  123. Reaven PD, Parthasarathy S, Beltz WF, Witztum JL. Effect of probucol dosage on plasma lipid and lipoprotein levels and on protection of low density lipoprotein against in vitro oxidation in humans. Arterioscler Thromb. 1992;12:318.

    Article  PubMed  CAS  Google Scholar 

  124. Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn A, Ganz P. The effect of cholesterol lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med. 1995;332:488.

    Article  PubMed  CAS  Google Scholar 

  125. Anderson TJ, Meredith IT, Charbonneau F, Yeung AC, Frei B, Selwyn AP, Ganz P. Endothelium-dependent coronary vasomotion relates to susceptibility of LDL to oxidation in humans. Circulation. 1996;93:1647.

    Article  PubMed  CAS  Google Scholar 

  126. Riemersma RA, Wood DA, Macintyre CCH, Elton RA, Gey KF, Oliver MF. Risk of angina pectoris and plasma concentrations of vitamins A, C, E, and carotene. Lancet. 1991;337:1.

    Article  PubMed  CAS  Google Scholar 

  127. Ramirez J, Flowers NC. Leukocyte ascorbic acid and its relationship to coronary artery disease in man. Am J Clin Nutr. 1980;33:2079.

    PubMed  CAS  Google Scholar 

  128. Vita JA, Keaney JF Jr, Raby KE, Morrow JD, Freedman JE, Lynch S, Koulouris SN, Hankin BR, Frei B. Low plasma ascorbic acid independently predicts the presence of an unstable coronary syndrome. J Am Coll Cardiol. 1998;31:980.

    Article  PubMed  CAS  Google Scholar 

  129. Nyyssönen K, Parviainen MT, Salonen R, Tuomilehto J, Salonen JT. Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland. Br Med J. 1997;314:634.

    Article  Google Scholar 

  130. Enstrom JE, Kanim LE, Klein MA. Vitamin C intake and mortality among a sample of the United States population. Epidemiology. 1992;3:194.

    Article  PubMed  CAS  Google Scholar 

  131. Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR. Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proc Natl Acad Sci USA. 1996;93:3704.

    Article  PubMed  CAS  Google Scholar 

  132. Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA. 1989;86:6377.

    Article  PubMed  CAS  Google Scholar 

  133. Jackson TS, Xu A, Vita JA, Keaney JF Jr. Ascorbate prevents the interaction of Superoxide and nitric oxide only at high physiologic concentrations. Circ Res. 1998;83:916.

    Article  PubMed  CAS  Google Scholar 

  134. Meister A. Glutathione-ascorbic acid antioxidant system in animals. J Biol Chem. 1994;269:9397.

    PubMed  CAS  Google Scholar 

  135. Levine GN, Frei B, Koulouris SN, Gerhard MD, Keaney JF Jr, Vita JA. Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation. 1996;96:1107.

    Article  Google Scholar 

  136. Gokce N, Keaney JF Jr., Frei B, Holbrook M, Olesiak M, Zachariah BJ, Leeuwenburgh C, Heinecke JW, Vita JA. Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation. 1999;99:3234.

    Article  PubMed  CAS  Google Scholar 

  137. Ito K, Akita H, Kanazawa K, Yamada S, Terashima M. Comparison of effects of ascorbic acid on endothelium-dependent vasodilation in patients with chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy versus patients with effort angina pectoris secondary to coronary artery disease. Am J Cardiol. 1998;82:762.

    Article  PubMed  CAS  Google Scholar 

  138. Hornig B, Arakawa N, Kohler C, Drexler H. Vitamin C improves endothelial function of conduit arteries in patients with chronic heart failure. Circulation. 1998;97:363.

    Article  PubMed  CAS  Google Scholar 

  139. Plotnick GD, Corretti MC, Vogel RA. Effect of antioxidant vitamins on the transient impairment of endothelium-dependent brachial artery vasoactivity following a single high-fat meal. JAMA. 1997;278:1682.

    Article  PubMed  CAS  Google Scholar 

  140. Ting HH, Timimi FK, Boles KS, Creager SJ, Ganz P, Creager MA. Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest. 1996;97:22.

    Article  PubMed  CAS  Google Scholar 

  141. Timimi FK, Ting HH, Haley EA, Roddy MA, Ganz P, Creager MA. Vitamin C improves endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol. 1998;31:552.

    Article  PubMed  CAS  Google Scholar 

  142. Ting HH, Timimi FK, Haley EA, Roddy MA, Ganz P, Creager MA. Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia. Circulation. 1997;95:2617.

    Article  PubMed  CAS  Google Scholar 

  143. Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A. Vitamin C improves endotheliumdependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation. 1997;97:2222.

    Article  Google Scholar 

  144. Sherman DL, Keaney JF Jr, Hankin B, Mannion T, Jewett T, Coffman JD, Vita JA. Ascorbic acid improves endothelial function in essential hypertension. Circulation. 1998;98:1–376 (abstract).

    Article  Google Scholar 

  145. Heitzer T, Just H, Munzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation. 1996;94:6.

    Article  PubMed  CAS  Google Scholar 

  146. Solzbach U, Hornig B, Jeserich M, Just H. Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation. 1997;96:1513.

    Article  PubMed  CAS  Google Scholar 

  147. Kugiyama K, Motoyama T, Hirashima O, Ohgushi M, Soejima H, Misumi K, Kawano H, Miyao Y, Yoshimura M, Ogawa H, Matsumura T, Sugiyama S, Yasue H. Vitamin C attenuates abnormal vasomotor reactivity in spasm coronary arteries in patients with coronary spastic angina. J Am Coll Cardiol. 1998;32:103.

    Article  PubMed  CAS  Google Scholar 

  148. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG. Angiotensin II-mediated hypertension in the rat increases vascular Superoxide production via membrane NADH/NADPH oxidase activation. J Clin Invest. 1996;97:1916.

    Article  PubMed  CAS  Google Scholar 

  149. Gotoh N, Niki E. Rates of interactions of Superoxide with vitamin E, vitamin C, and related compounds as measured by chemiluminescence. Biochim Biophys Acta. 1992;1115:201.

    Article  PubMed  CAS  Google Scholar 

  150. Huie RE, Padmaja S. The reaction of NO with Superoxide. Free Radic Res Commun. 1993;18:195.

    Article  PubMed  CAS  Google Scholar 

  151. Malinski T, Taha Z, Grunfeld S, Patton S, Kapturczak M, Tomboulian P. Diffusion of nitric oxide in the aorta wall monitored in situ by porphyrinic microsensors. Biochem Biophys Res Commun. 1993;193:1076.

    Article  PubMed  CAS  Google Scholar 

  152. Dabbagh AJ, Frei B. Human suction blister interstitial fluid prevents metal ion-dependent oxidation of low density lipoprotein by macrophages and in cell-free systems. J Clin Invest. 1995;96:1958.

    Article  PubMed  CAS  Google Scholar 

  153. Howells DW, Hyland K. Direct analysis of tetrahydrobiopterin in cerebrospinal fluid by highperformance liquid chromatography with redox electrochemistry: Prevention of autooxidation during storage and analysis. Clin Chim Acta. 1987;167:23.

    Article  PubMed  CAS  Google Scholar 

  154. Stroes E, Kastelein J, Cosentino F, Erkelens W, Wever R, Koomans H, Luscher T, Rabelink T. Tetrahydrobiopterin restores endothelial function in hypercholesterolemia. J Clin Invest. 1997;99:41.

    Article  PubMed  CAS  Google Scholar 

  155. Kashiba-Iwatsuki M, Yamaguchi M, Inoue M. Role of ascorbic acid in the metabolism of S-nitroso-glutathione. FEBS Lett. 1996, 389:149.

    Article  PubMed  CAS  Google Scholar 

  156. Anderson ME. Glutathione and glutathione delivery compounds, in Sies H (ed): Antioxidants in disease mechanisms and therapy, Advances in Pharmacology ed. San Diego, CA, Academic Press, 1997, vol 38, pp. 65–78.

    Google Scholar 

  157. Murphy ME, Piper H-M, Watanabe H, Sies H. Nitric oxide production by cultured aortic endothelial cells in response to thiol depletion and replenishment. J Biol Chem. 1991;266:19378.

    PubMed  CAS  Google Scholar 

  158. Ghigo D, Alessio P, Foco A, Bussolino F, Costamagna C, Heller R, Garbarino G, Pescarmona GP, Bosia A. Nitric oxide synthesis is impaired in glutathione-depleted human umbilical vein endothelial cells. Am J Physiol. 1993;265:C728.

    PubMed  CAS  Google Scholar 

  159. Komori Y, Hyun J, Chiang K, Fukuto JM. The role of thiols in the apparent activation of rat brain nitric oxide synthase (NOS). J Biochem. 1995;117:923.

    PubMed  CAS  Google Scholar 

  160. Stuehr DJ, Kwon NS, Nathan CF. FAD and GSH participate in macrophage synthesis of nitric oxide. Biochem Biophys Res Commun. 1990;168:558.

    Article  PubMed  CAS  Google Scholar 

  161. Stamler JS, Singel DJ, Loscalzo J. Biochemistry of nitric oxide and its redox-activated forms. Science. 1992;258:1898.

    Article  PubMed  CAS  Google Scholar 

  162. Patel JM, Abeles AJ, Block ER. Nitric oxide exposure and sulfhydryl modulation alter L-arginine transport in cultured pulmonary artery endothelial cells. Free Rad Biol Med. 1996;20:629.

    Article  PubMed  CAS  Google Scholar 

  163. Ma XL, Lopez BL, Liu GL, Christopher TA, Gao F, Guo Y, Feuerstein GZ, Ruffolo RR Jr, Barone FC, Yue TL. Hypercholesterolemia impairs a detoxification mechanism against peroxynitrite and renders the vascular tissue more susceptible to oxidative injury. Circ Res. 1997;80:894.

    Article  PubMed  CAS  Google Scholar 

  164. Kuzuya M, Naito M, Funaki C, Hayashi T, Asai K, Kuauya F. Protective role of intracellular glutathione against oxidized low density lipoprotein in cultured endothelial cells. Biochem Biophys Res Commun. 1989;163:1466.

    Article  PubMed  CAS  Google Scholar 

  165. Porta P, Aebi S, Summer K, Lauterburg BH. L-2-oxothiazolidine-4-carboxylic acid, a cysteine prodrug: Pharmacokinetics and effects on thiols in plasma and lymphocytes in humans. J Pharmacol Exp Ther. 1991,257:331.

    PubMed  CAS  Google Scholar 

  166. Vita JA, Frei B, Holbrook M, Gokce N, Leaf C, Keaney JF Jr. L-2-oxothiazolidine-4-carboxylic acid reverses endothelial dysfunction in patients with coronary artery disease. J Clin Invest. 1998;101:1408.

    Article  PubMed  CAS  Google Scholar 

  167. Kugiyama K, Ohgushi M, Motoyama T, Hirashima O, Soejima H, Misumi K, Yoshimura M, Ogawa H, Sugiyama S, Yasue H. Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation. Circulation. 1998;97:2299.

    Article  PubMed  CAS  Google Scholar 

  168. Prasad A, Padder F, Andrews NP, Husain M, Mincemoyer R, Panza JA, Quyyumi AA. Glutathione and N-acetylcysteine improve endothelial dysfunction in humans. Circulation. 1998;96:1-251 (abstract).

    Google Scholar 

  169. Creager MA, Roddy MA, Boles K, Stamler JS. N-acetylcysteine does not influence the activity of endothelium-derived relaxing factor in vivo. Hypertension. 1997;29:668.

    Article  CAS  Google Scholar 

  170. Marui N, Offermann MK, Swerlick R, Kunsch C, Rosen C, Ahmad M, Alexander RW, Medford RM. 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;92:1866.

    Article  PubMed  CAS  Google Scholar 

  171. Marklund SL, Nilsson P, Israelsson K, Schampi I, Peltonen M, Asplund K. Two variants of extracellular-superoxide dismutase: relation to cardiovascular risk in an unselected middle-aged population. J Intern Med. 1997;242:5.

    Article  PubMed  CAS  Google Scholar 

  172. Freedman JE, Loscalzo J, Benoit SE, Valeri CR, Barnard MR, Michelson AD. Decreased platelet inhibition by nitric oxide in two brothers with a history of arterial thrombosis. J Clin Invest. 1996;97:979.

    Article  PubMed  CAS  Google Scholar 

  173. Nakazono K, Watanabe N, Matsuno K, Sasaki J, Sato T, Inoue M. Does Superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci USA. 1991;88:10045.

    Article  PubMed  CAS  Google Scholar 

  174. Meredith IT, Anderson TJ, Yeung AC, Lieberman EH, Dyce MC, Gonenne A, Uehata A, Selwyn AP, Ganz P. Superoxide dismutase restores endothelial vasodilator function in human coronary arteries in vivo. Circulation. 1993;88:1–467.

    Google Scholar 

  175. Garcia C, Kilcoyne CM, Cardillo C, Cannon RO III, Quyyumi AA, Panza JA. Effect of copperzinc Superoxide dismutase on endothelium-dependent vasodilation in patients with essential hypertension. Hypertension. 1995;26:863.

    Article  PubMed  CAS  Google Scholar 

  176. Garcia CE, Kilcoyne CM, Cardillo C, Cannon RO 3rd, Quyyumi AA, Panza JA. Evidence that endothelial dysfunction in patients with hypercholesterolemia is not due to increased extracellular nitric oxide breakdown by Superoxide anions. Am J Cardiol. 1995;76:1157.

    Article  PubMed  CAS  Google Scholar 

  177. Flaherty JT, Pitt B, Gruber JW, Heuser RR, Rothbaum DA, Burwell LR, George BS, Kereiakes DJ, Deitchman D, Gustafson N, Brinker JA, Becker LC, Mancini J, Topol E, Wems SW. Recombinant human Superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction. Circulation. 1994;89:1982.

    Article  PubMed  CAS  Google Scholar 

  178. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801.

    Article  PubMed  CAS  Google Scholar 

  179. Heller R, Münscher-Paulig, F.; Gräbner, R; Till, U. Ascorbic acid potentiates nitric oxide synthesis in endothelial cells. J Biol. Chem 1999;274:8254

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Elizabeth S. Biegelsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph A. Vita
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Boston University School of Medicine, Boston, MA, USA

    John F. Keaney Jr. M.D. (Associate Professor of Medicine and Pharmacology) (Associate Professor of Medicine and Pharmacology)

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media New York

About this chapter

Cite this chapter

Biegelsen, E.S., Vita, J.A. (2000). Human Studies of Antioxidants and Vascular Function. In: Keaney, J.F. (eds) Oxidative Stress and Vascular Disease. Developments in Cardiovascular Medicine, vol 224. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4649-8_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4649-8_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7103-8

  • Online ISBN: 978-1-4615-4649-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation