Advertisement

Prevention of Atherosclerosis: Endothelial Function, Cholesterol, and Antioxidants

  • Robert A. Vogel
Part of the Basic Science for the Cardiologist book series (BASC, volume 2)

Abstract

Although age-adjusted mortality from atherosclerosis-related diseases has declined significantly in the United States and some European countries over the past four decades, it has recently become the world’s leading cause of death, exceeding infectious diseases. Considerable epidemiologic, clinical, and experimental data suggest a causative relationship between coronary risk factors, especially hypercholesterolemia, and atherosclerotic cardiovascular disease. Coronary and other atherosclerosis have traditionally been thought to result from cholesterol deposition, modification, and macrophage uptake leading to vascular smooth muscle cell proliferation and matrix formation. Cardiovascular events subsequently arise from plaque rupture or ulceration with ensuing partial or complete vessel occlusion. Recently, the vasculature has been found to be an active and complex organ rather than a passive conduit. The endothelium is now known to be an important regulator of vascular tone, lipid breakdown, thrombogenesis, inflamation, and vessel growth. In the presence of risk factors such as hypercholesterolemia, the endothelium promotes atherosclerosis through vasoconstriction, monocyte and platelet adhesion, thrombogenesis, and growth factor release. This dysfunctional state appears before the earliest anatomic evidence of atherosclerosis. Hypercholesterolemia and the other risk factors have been shown to reduce nitric oxide availability, the predominate endothelium-derived vasodilator.

Keywords

Nitric Oxide Endothelial Function Cholesterol Lowering Coronary Risk Factor Hypercholesterolemic Rabbit 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Anitschkow N: Experimental atherosclerosis in animals. In Cowdry EV (ed) Arteriosclerosis.ASurvey of the Problem. New York, Macmillan, 1933, pp 271–322.Google Scholar
  2. 2.
    Gordon T, Kannel WB. Premature mortality from coronary heart disease. The Framinghan Heart Study. JAMA 1971;215:1617–25.PubMedCrossRefGoogle Scholar
  3. 3.
    Keys A, Araranis C, Blackburn H, et al. Epidemiologie studies related to coronary heart disease: Characteristics of men aged 40-59 in seven countries. Acta Med Scand 1967;180(Suppl 460):1–392.Google Scholar
  4. 4.
    The Multiple Risk Factor Intervention Trial Research Group. Mortality rates after 10.5 years for participants in the Multiple Risk Factor Intervention Trial. Findings related to a priori hypothesis of the trial. JAMA 1990;263:1795–1801.CrossRefGoogle Scholar
  5. 5.
    Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial Result. I. Reduction in incidence of coronary heart disease. JAMA 1984;251:351–64.CrossRefGoogle Scholar
  6. 6.
    Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial Results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984;25:365–74.Google Scholar
  7. 7.
    Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: Primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987;317:1237–45.PubMedCrossRefGoogle Scholar
  8. 8.
    Brown BG, Zhao X-Q, Sacco DE, Albers JJ. Lipid lowering and plaque regression. New insights into prevention of plaque disruption and clinical events in coronary disease. Circulation 1993;87:1781–89.PubMedGoogle Scholar
  9. 9.
    Gotto AM Jr. Results of recent large cholesterol-lowering trials and their implications for clinical management. Am J Cardiol 1997;79:1663–1669.PubMedCrossRefGoogle Scholar
  10. 10.
    Ross R. The pathogenesis of atherosclerosis. N Engl J Med 1986;314:488–500.PubMedCrossRefGoogle Scholar
  11. 11.
    Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989;320:915–24.PubMedCrossRefGoogle Scholar
  12. 12.
    Segrest JP, Anantharamaiah GM. Pathogenesis of atherosclerosis. Curr Opinion Cardiol 1994;9:404–10.Google Scholar
  13. 13.
    McGorisk GM, Treasure CB. Endothelial dysfunction and coronary heart disease. Curr Opin Cardiol 1996;11:341–350.PubMedCrossRefGoogle Scholar
  14. 14.
    Abrams J. Role of endothelial dysfunction in coronary artery disease. Am J Cardiol 1997;79(12B):2–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Vogel RA. Coronary risk factors, endothelial function, and atherosclerosis: a review. Clin Cardiol 1997;20:426–32.PubMedGoogle Scholar
  16. 16.
    Luscher TF, Barton M. Biology of the endothelium. Clin Cardiol 1997;20(suppl II):II-3–II-10.Google Scholar
  17. 17.
    Celermajer DS. Endothelial dysfunction: Does it matter? Is it reversible? J Am Coll Cardiol 1997;30:325–333.PubMedCrossRefGoogle Scholar
  18. 18.
    Gibbons GH. Endothelial function as a determinant of vascular function and structure: anew theraputic target. Am J Cardiol 1997;79(5A):3–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Cooke JP, Tsao PS. Is NO an endogenous antiatherosclerotic molecule? Arterioscler Thromb 1994;14:653–655.PubMedGoogle Scholar
  20. 20.
    Candipan RC, Wang B-Y, Buitrago R, Cooke JP. Regression or progression. Dependency on vascular nitric oxide. Arterioscler Thromb Vasc Biol 1996;16:44–50.PubMedGoogle Scholar
  21. 21.
    Wever RMF, Luscher TF, Cosentino F, Rabelink TJ. Atherosclerosis and the two faces of endothelial nitric oxide synthase. Circulation 1998;97:108–112.PubMedGoogle Scholar
  22. 22.
    Harrison DG. Endothelial fonction and oxidant stress. Clin Cardiol 1997;20(suppl II):II-11–II-17.Google Scholar
  23. 23.
    Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373–76.PubMedCrossRefGoogle Scholar
  24. 24.
    Mocada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002–12.CrossRefGoogle Scholar
  25. 25.
    Vane JR, Anggard EE, Botting RM. Regulatory fonctions of the vascular endothelium. NEngl J Med 1990;323:27–36.CrossRefGoogle Scholar
  26. 26.
    Lerman A, Burnett JC Jr. Intact and altered endothelium in regulation of vasomotion. Circulation 1992;86(suppl III):III-12–III-19.Google Scholar
  27. 27.
    Flavahan NA. Atherosclerosis or lipoprotein-induced endothelial dysfunction. Potential mechanisms underlying reduction in EDRF/nitric oxide activity. Circulation 1992;85:1927–38.PubMedGoogle Scholar
  28. 28.
    Dzau VJ, Gibbons GH, Cooke JP, Omoigui N. Vascular biology and medicine in the 1990’s: scope, concepts, potentials, and perspectives. Circulation 1993;87:705–719.PubMedGoogle Scholar
  29. 29.
    Gibbons GH, Dzau VJ. The emerging concept of vascular remodeling. N Engl J Med 1994;330:1431–1438.PubMedCrossRefGoogle Scholar
  30. 30.
    Levine GN, Keaney JF Jr, Vita JA. Cholesterol reduction in cardiovascular disease. Clinical benefits and possible mechanisms. N Engl J Med 1995;332:512–521.PubMedCrossRefGoogle Scholar
  31. 31.
    Flavahan NA, Vanhoutte PM. Endothelium-derived hyperpolarizing factor. Blood Vessels 1990;27:238–245.Google Scholar
  32. 32.
    Cohen RA, Vanhouette PM. Endothelium-dependent hyperpolarization. Beyond nitric oxide and cyclic GMP. Circulation 1995;92:3337–3349.PubMedGoogle Scholar
  33. 33.
    Lerman A, Hildebrand FL Jr, Margulies KB, O’Murchu B, Perella MA, Heublin DM, Schwab TR, Burnett JC. Endothelin: a new cardiovascular regulatory peptide. Mayo Clin Proc 1990;65:1441–1455.PubMedGoogle Scholar
  34. 34.
    Yanagisawa M. The endothelin system. A new target for theraputic intervention. Circulation 1994:89:1320–1322.PubMedGoogle Scholar
  35. 35.
    Gibbons GH. Vasculoprotective and cardioprotective mechanisms of angiotensin-converting enzyme inhibition: the homeostatic balance between angiotensin II and nitric oxide. Clin Cardiol 1997;20(suppl II):II-18–II-25.Google Scholar
  36. 36.
    Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. NEngl J Med 1986;315:1046–51.CrossRefGoogle Scholar
  37. 37.
    Cox DA, Vita JA, Treasure CB, Fish D, Alexander RW, Ganz P, Selwyn AP. Atherosclerosis impairs flow-mediated dilation of human coronary arteries. Circulation 1989;80:458–465PubMedGoogle Scholar
  38. 38.
    Drexler H, Zeiher AM, Wollschlager H, Meinertz T, Just H, Bonzel T. Flow-dependent coronary artery dilatation in humans. Circulation 1989;80:466–74.PubMedGoogle Scholar
  39. 39.
    Werns SW, Walton JA, Hsia HH, Nabel EG, Sanz ML, Pitt B. Evidence of endothelial dysfunction in angiographically normal coronary arteries of patients with coronary artery disease. Circulation 1989;79:287–91.PubMedGoogle Scholar
  40. 40.
    Vogel RA. Endothelium-dependent vasoregulation of coronary artery diameter and blood flow. Circulation 1993;88:325–27.PubMedGoogle Scholar
  41. 41.
    Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340:1111–15.PubMedCrossRefGoogle Scholar
  42. 42.
    Corretti MC, Plotnick GD, Vogel RA. Technical aspects of evaluating brachial artery vasodilation using high-frequency ultrasound. Am J Physiol 1995;268 (Heart Circ Physiol 37):H1397–H1404.PubMedGoogle Scholar
  43. 43.
    Sorensen KE, Celermajer DS, Spiegelhalter DJ, et al. Non-invasive measurement of human endothelium dependent responses: accuracy and reproducibility. Br Heart J 1995;74:247–253.PubMedCrossRefGoogle Scholar
  44. 44.
    Anderson TJ, Uehata A, Gerhard MD, et al. Close relationship of endothelial fonction in the human coronary and peripheral circulations. J Am Coll Cardiol 1995;26:1235–41.PubMedCrossRefGoogle Scholar
  45. 45.
    Zeiher AM, Krause T, Schachinger V, Minners J, Moser E. Impaired endothelium-dependent vasodilation of coronary resistance vessels is associated with exercise-induced myocardial ischemia. Circulation 1995;91. 2345–52.PubMedGoogle Scholar
  46. 46.
    Egashira K, Hirooka Y, Kuga T, Mohri M, Takeshita A. Effects of L-arginine supplementation on endothelium-dependent caronary vasodilation in patients with angina pectoris and normal coronary arteries. Circulation 1996;94:130–134.PubMedGoogle Scholar
  47. 47.
    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;91:1314–1319.PubMedGoogle Scholar
  48. 48.
    Shiode N, Morishima N, Nakayama K, Yamagata T, Matsuura H, Kajiyama G. Flow-mediated vasodilation of human epicardial coronary arteries: effect of inhibition of nitric oxide synthesis. J Am Coll Cardiol 1996;27:304–310.PubMedCrossRefGoogle Scholar
  49. 49.
    Lefroy DC, Crake T, Uren NG, Davies GJ, Maseri A. Effect of inhibition of nitric oxide synthesis on epicardial coronary artery caliber and coronary blood flow in humans. Circulation 1993;88:43–54.PubMedGoogle Scholar
  50. 50.
    Gilligan DM, Guetta V, Panza JA, Garcia CE, Quyyumi AA, Cannon RO III. Selective loss of microvascular endothelial function in human hypercholesterolemia. Circulation 1994;90:35–41.PubMedGoogle Scholar
  51. 51.
    Shiode N, Nakayama K, Morishima N, et al. Nitric oxide production by coronary conductance vessels in hypercholesterolemic patients. Am Heart J 1996;131:1051–57.PubMedCrossRefGoogle Scholar
  52. 52.
    El-Tamimi H, Mansour M, Wargovich TJ, et al. Constrictor and dilator responses to intracoronary acetylcholine in adjacent segments of the same coronary artery in patients with coronary artery disease. Circulation 1994;89:45–51.PubMedGoogle Scholar
  53. 53.
    Penny WF, Rockman H, Long J, et al. Heterogeneity of vasomotor response to acetylcholine along the human coronary artery. J Am Coll Cardiol 1995;25:1046–55.PubMedCrossRefGoogle Scholar
  54. 54.
    Kuo L, Davis MJ, Chilian WM. Longitudinal gradients for endothelium-dependent and independent vascular responses in the coronary microcirculation. Circulation 1995;92:518–25PubMedGoogle Scholar
  55. 55.
    Tagawa T, Imaizumi T, Endo T, Shiramoto M, Harasawa Y, Takeshita A. Role of nitric oxide in reactive hyperemia in human forearm vessels. Circulation 1994;90:2285–2290.PubMedGoogle Scholar
  56. 56.
    Reddy KG, Nair RN, Sheehan HM, Hodgson J McB. Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J Am Coll Cardiol 1994;23:833–43.PubMedGoogle Scholar
  57. 57.
    Mano T, Masuyama T, Yamamoto K, et al. Endothelial dysfunction in the early stage precedes appearance of intimai lesions assessable with intravascular ultrasound. Am Heart J 1996;131;231–38.PubMedCrossRefGoogle Scholar
  58. 58.
    Vita JA, Treasure CB, Nabel EG, McLenachan JM, Fish D, Yeung AC, Vekshtein VI, Selwyn AP, Ganz P. Coronary vasomotor responses to acetylcholine relates to risk factors for coronary artery disease. Circulation 1990;81:491–97.PubMedGoogle Scholar
  59. 59.
    Seiler C, Hess M, Buechi M, Suter TM, Krayenbuehl HP. Influence of serum cholesterol and other coronary risk factors on vasomotion of angiographically normal coronary arteries. Circulation 1993;88 (part l):2139–48.PubMedGoogle Scholar
  60. 60.
    Panza JA, Casino PR, Kilcoyne CM, et al. Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 1993;87:1468–74.PubMedGoogle Scholar
  61. 61.
    Celermajer DS, Sorensen KE, Georgakopoulos D, et al. Cigarette smoking is associated withdose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 1993;88:2149–55.PubMedGoogle Scholar
  62. 62.
    Johnstone MT, Creager SJ, Scales KM, et al. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation 1993;88:2510–16.PubMedGoogle Scholar
  63. 63.
    Egashira K, Inou T, Hirooka Y, et al. Effects of age on endothelium-dependent vasodilation of resistance coronary artery by acetylcholine in humans. Circulation 1993;88:77–81.PubMedGoogle Scholar
  64. 64.
    Celermaher DS, Sorensen KE, Spiegelhalter DJ, et al. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol 1994;24:471–76.Google Scholar
  65. 65.
    Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol 1994;24:1468–74.PubMedGoogle Scholar
  66. 66.
    Taddei S, Virdis A, Mattei P, et al. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation 1995;91:1981–87.PubMedGoogle Scholar
  67. 67.
    Celermajer DS, Adams MR, Clarkson P, et al. Passive smoking and impaired endothelium-dependent arteriial dilatation in healthy young adults. N Engl J Med 1996;334:150–54.PubMedCrossRefGoogle Scholar
  68. 68.
    Heitzer T, Yla-Herttuala S, Kurz S, et al. Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia. Role of oxidized LDL. Circulation 1996;1346–53.Google Scholar
  69. 69.
    Glasser SP, Selwyn AP, Ganz P. Atherosclerosis: risk factors and the vascular endothelium. Am Heart J 1996;131:379–84.PubMedCrossRefGoogle Scholar
  70. 70.
    Egashira K, Hirooka Y, Kai H, Sugimachi M, Suziki S, Inou T, Takeshita A.. Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Circulation 1994;89:2519–24.PubMedGoogle Scholar
  71. 71.
    Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn AP, Ganz P. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med 1995;332:488–93.PubMedCrossRefGoogle Scholar
  72. 72.
    Treasure CB, Klein JL, Weintraub WS, Talley JD, Stillabower ME, Kosinski A, Zhang J, Boccuzzi SJ, Cedarholm JC, Alexander RW. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med 1995;332:481–87.PubMedCrossRefGoogle Scholar
  73. 73.
    Drury J, Cohen JD, Veenendrababu B, et al. Brachial artery endothelium dependent vasodilation in patients enrolled in the cholesterol and recurrent events (CARE) study. Circulation 1996;94(suppl I):I–402 (abstr).Google Scholar
  74. 74.
    Osborne JA, Siegman MJ, Sedar AW, Mooers SU, Lefer AM. Lack of endothelium-dependent relaxation in coronary resistance arteries of cholesterol-fed rabbits. Am J Physiol 1989;256:C591–C597.PubMedGoogle Scholar
  75. 75.
    Shimokawa AH, Vanhoutte PM. Hypercholesterolemia causes generalized impairment of endothelium-dependent relaxation to aggregating platelets in porcine arteries. J Am Coll Cardiol 1989;13:1402–1408PubMedGoogle Scholar
  76. 76.
    Kugiyama K, Kerns SA, Morisett JD, et al. Impairment of endothelium-dependent-relaxation by lysolecithin in modified low-density lipoproteins. Nature 1990;334:160–62.CrossRefGoogle Scholar
  77. 77.
    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;86:228–34.PubMedGoogle Scholar
  78. 78.
    Vogel RA, Corretti MC. Estrogens, progestins, and heart disease. Can endothelial function devine the benefit? Circulation 1998;97:1223–1226.PubMedGoogle Scholar
  79. 79.
    Steinberg HO, Bayazeed B, Hook G, Johnson A, Cronin J, Baron AD. Endothelial dysfunction is associated with cholesterol levels in the high normal range in humans. Circulation 1997;96:3287–3293.PubMedGoogle Scholar
  80. 80.
    Creager MA, Selwyn A. When “normal” cholesterol levels injure the endothelium. Circulation 1997;96:3255–3257.PubMedGoogle Scholar
  81. 81.
    Simon BC, Cunningham LD, Cohen RA. Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery. J Clin Invest 1990;86:75–79.PubMedGoogle Scholar
  82. 82.
    Chin JH, Azhan S, Hoffman BB. Inactivation of endothelial derived relaxing factor by oxidized lipoproteins. J Clin Invest 1992;89:10–18.PubMedGoogle Scholar
  83. 83.
    Galle J, Bengen J, Schollmeyer P, Wanner C. Impairment of endothelium-dependent dilation in rabbit renal arteries by oxidized lipoprotein(a). Role of oxygen-derived radicals. Circulation 1995;92:1582–1589.PubMedGoogle Scholar
  84. 84.
    Anderson TJ, Meredith IT, Charbonneau F, Yeung AC, Frei B, Selwyn AP, Ganz P. Endothelium-dependent coronary vasomotion relates to the susceptibility of LDL to oxidation in humans. Circulation 1996;93:1647–50.PubMedGoogle Scholar
  85. 85.
    Chen LY, Mehta P, Mehta JL. Oxidized LDL decreases L-arginine uptake and nitric oxide protein expression in human platelets. Relevance of the effect of oxidized LDL on platelet function. Circulation 1996;93:1740–1746.PubMedGoogle Scholar
  86. 86.
    Raitakari OT, Pitkanen O-P, Lehtimaki T, et al. In vivo low density lipoprotein oxidation relates to coronary reactivity in young men. J Am Coll Cardiol 1997;30:97–102.PubMedCrossRefGoogle Scholar
  87. 87.
    Casino PR, Kilcoyne CM, Quyyumi AA, Hoeg JM, Panza JA. The role of nitric oxide in endothelium-dependent vasodilation of hypercholesterolemic patients. Circulation 1993;88:2541–2547.PubMedGoogle Scholar
  88. 88.
    Quyyumi AA, Mulcahy D, Andrews NP, Husain S, Panza JA, Cannon RO III. Coronary vascular nitric oxide activity in hypertension and hypercholesterolemia. Circulation 1997;95:104–110.PubMedGoogle Scholar
  89. 89.
    Matsuda Y, Hirata K, Inoue N, et al. High density lipoprotein reverses inhibitory effect of oxidized low density lipoprotein on endothelium-dependent arterial relaxation. Circ Res 1993;72:1103–1109.PubMedGoogle Scholar
  90. 90.
    Kuhn FE, Mohler ER, Reagan K, Reagan K, Lu DY, Rackley CE. Effects of high-density lipoprotein on acetylcholine-induced coronary vasoreactivity. Am J Cardiol 1991;68:1425–1430.PubMedCrossRefGoogle Scholar
  91. 91.
    Hackman A, Abe Y, Insull W, Pownall H, Smith L, Dunn K, Gotto AM Jr, Ballantyne CM. Levels of soluble adhesion molecules in patients with dyslipidemia. Circulation 1996;93:1334–1338.PubMedGoogle Scholar
  92. 92.
    Sampietro T, Tuomi M, Ferdeghini M, Ciardi A, Marraccini P, Prontera C, Sassi G, Taddei M, Bionda A. Plasma cholesterol regulates soluble cell adhesion molecule expression in familiar hypercholesterolemia. Circulation 1997;96:1381–1385.PubMedGoogle Scholar
  93. 93.
    Lacoste L, Lam JYT, Hung J, et al. Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation 1995;92:3172–3177PubMedGoogle Scholar
  94. 94.
    Nofer J-R, Tepel M, Kehrel B, et al. Low-density lipoproteins inhibit the Na+/H+ antiport in human platelets. A novel mechanism enhancing platelet activity in hypercholesterolemia. Circulation 1997;95:1370–77.PubMedGoogle Scholar
  95. 95.
    Vogel RA, Corretti MC, Plotnick GD. Effect of a single high-fat meal on endothelial function in healthy subjects. Am J Cardiol 1997;79:350–54.PubMedCrossRefGoogle Scholar
  96. 96.
    Plotnick GD, Corretti MC, Vogel RA. Effect of antioxidant vitamins on the transient impairment of endothelium-dependent vasoactivity following a single high-fat meal. JAMA 1997;278:1682–1686.PubMedCrossRefGoogle Scholar
  97. 97.
    Lundman P, Eriksson M, Schenck-Gustafsson K, Karpe F, Tornvall P. Transient triglyceridemia decreases vascular reactivity in young, healthy men without risk factors for coronary heart disease. Circulation 1997;96:3266–3268.PubMedGoogle Scholar
  98. 98.
    Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A, Bayazeed B, Baron AD. Elevated circulating free fatty acids impair endothelium-dependent vasodilation. J Clin Invest 1997;100:1230–1239PubMedGoogle Scholar
  99. 99.
    Malis CD, Leaf A, Varadarajan GS, Newell JB, Weber PC, Force T, Bonventre JV. Effects of dietary ϖ3 fatty acids on vascular contractility in preanoxic and postanoxic aortic rings. Circulation 1991;84:1393–1401.PubMedGoogle Scholar
  100. 100.
    Goode GK, Garcia S, Heagerty AM. Dietary supplementation with marine fish oil improves in vitro small artery endothelial function in hypercholesterolemic patients, Circulation 1997;96:2802–2807.PubMedGoogle Scholar
  101. 101.
    Larsen LF, Bladbjerg E-E, Jespersen J, Markmann P. Effects of dietary fat quality and quantity on postprandial activation of blood coagulation factor VII. Arterioscl Thromb Vasc.Biol 1997; 17:2904–2909.PubMedGoogle Scholar
  102. 102.
    Chowienczyk PJ, Watts GF, Wierzbicki AS, Cockcroft JR, Brett SE, Ritter JM. Preserved endothelial function in patients with severe hypertriglyceridemia and low functional lipoprotein lipase activity. J Am Coll Cardiol 1997;29:964–968.PubMedCrossRefGoogle Scholar
  103. 103.
    Yokoyama I, Ohtake T, Momomura S-I, Yonekura K, Nishikawa J, Sasaki Y, Omata M. Impaired myocardial vasodilation during hyperemic stress with dipyridamole in hypertriglyceridemia. J Am Coll Cardiol 1998;31:1568–1574.PubMedCrossRefGoogle Scholar
  104. 104.
    Williams SB, Goldfine AB, Timimi FK, Ting HH, Roddy M-A, Simonson DC, Creager MA. Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation 1998;97:1695–1701.PubMedGoogle Scholar
  105. 105.
    Kugiyama K, Doi H, Motoyama T, Soejima H, Misumi K, Kawano H, Nakagawa O, Yoshimura M, Ogawa H, Matsumura T, Sugiyama S, Nakano T, Nakajima K, Yasue H. Association of remnant lipoprotein levels with impairment of endothelium-dependent vasomotor function in human coronary arteries. Circulation 1998;97:2519–2526.PubMedGoogle Scholar
  106. 106.
    Masuoka H, Ishikura K, Kamei S, Obe T, Seko T, Okuda K, Koyabu S, Tsuneoka K, Tamai T, Sugawa M, Nakano T. Predictive value of remnant-like particles cholesterol/high-density lipoprotein cholesterol as a new indicator of coronary artery disease. Am Heart J 1998; 136:226–230.PubMedCrossRefGoogle Scholar
  107. 107.
    Osborne JA, Lento PH, Siegfried MR, Stahl GL, Fusman B, Lefer AM. Cardiovascular effects of acute hypercholesterolemia. Reversal with lovastatin treatment. J Clin Invest 1989;83:465–473.PubMedGoogle Scholar
  108. 108.
    Leung W-H, Lau C-P, Wong C-K. Beneficial effect of cholesterol-lowering therapy on coronary endothelium-dependent relaxation in hypercholesterolaemic patients. Lancet 1993;341:1496–500.PubMedCrossRefGoogle Scholar
  109. 109.
    Vogel RA, Corretti MC, Plotnick GP. Changes in flow-mediated brachial artery vasoactivity with lowering of desirable cholesterol levels in healthy middle-aged men. Am J Cardiol 1996;77:37–40.PubMedCrossRefGoogle Scholar
  110. 110.
    Seiler C, Suter TM, Hess OM. Exercise-induced vasomotion of angiographically normal and stenotic coronary arteries improves after cholesterol-lowering drug therapy with bezafibrate. J Am Coll Cardiol 1995;26:1615–22.PubMedCrossRefGoogle Scholar
  111. 111.
    Goode GK, Heagerty AM. In vitro responses of human peripheral small arteries in hypercholesterolemia and effects of therapy. Circulation 1995;91:2898–2903.PubMedGoogle Scholar
  112. 112.
    Stroes ESG, Koomans HA, de Bruin TWA, et al. Vascular function in the forearm of hypercholesterolaemic patients off and on lipid-lowering medication. Lancet 1995;346:467–71.PubMedCrossRefGoogle Scholar
  113. 113.
    Yeung A, Hodgson JMcB, Winniford M, et al. Assessment of coronary vascular reactivity after cholesterol lowering. Circulation 1996;94(suppl I):I–402 (abstr)Google Scholar
  114. 114.
    Tamai O, Matsuoka H, Itabe H, Wada Y, Kohno K, Imaizumi T. Single LDL aphesesis improves endothelium-dependent vasodilatation in hypercholesterolemic humans. Circulation 1997;95:76–82.PubMedGoogle Scholar
  115. 115.
    O’Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month. Circulation 1997;95:1126–1131.PubMedGoogle Scholar
  116. 116.
    Andrews TC, Whitnet EJ, Green G, Kalenian R, Personius BE. Effect of gemfibrozil ± niacin ± cholestyramine on endothelial function in patients with serum low-density lipoprotein cholesterol levels <160 mg/dl and high-density lipoprotein cholesterol levels < 40 mg/dl. Am J Cardiol 1997;80:831–835.PubMedCrossRefGoogle Scholar
  117. 117.
    Vogel RA, Corretti MC, Plotnick GD. The mechanism of improvement in endothelial function by pravastatin: direct effect or through cholesterol lowering. J Am Coll Cardiol 1998;31:60A.CrossRefGoogle Scholar
  118. 118.
    Chen L, Haught WH, Yang B, Saldeen TGP, Parathasarathy S, Mehta J. Preservation of endogenous antioxidant activity and inhibition of lipid peroxidation as common mechanisms of antiatherosclerotic effects of vitamin E, lovastatin and amlodipine. J Am Coll Cardiol 1997;30:569–575PubMedCrossRefGoogle Scholar
  119. 119.
    Weber C, Erl W, Weber KSC, Weber PC. HMG-CoA reductase inhibitors decrease CD1 lb expression and CD1 1b-dependent adhesion to endothelium and reduce increased adhesiveness of monocytes isolated from patients with hypercholesterolemia. J Am Coll Cardiol 1997;30:1212–1217.PubMedCrossRefGoogle Scholar
  120. 120.
    Gould KL, Ornish D, Scherwitz L, et al. Changes in myocardial perfusion abnormalities by positron emission tomography afetr long-term, intense risk factor modification. JAMA 1995;274:894–901.PubMedCrossRefGoogle Scholar
  121. 121.
    van Boven AJ, Jukema JW, Zwinderman AH, et al. Reduction of transient myocardial ischemia with pravastatin in addition to the conventional treatment in patients with angina pectoris. Circulation 1996;94:1503–1505.PubMedGoogle Scholar
  122. 122.
    Aengevaeren WRM, Uijen GRH, Jukema JW, Bruschke AVG, van der Werf T. Functional improvement by pravastatin in the regression growth evaluation statin study (REGRESS). Circulation 1997;96:429–435.PubMedGoogle Scholar
  123. 123.
    Andrews TC, Raby K, Barry J, et al. Effect of cholesterol reduction on myocardial ischemia in patients with coronary disease. Circulation 1997;95:324–28.PubMedGoogle Scholar
  124. 124.
    Drexler H, Zeiher AM, Meinzer K, Just H. Correction of endothelial dysfunction in coronary microcirculation of hypercholesterolaemic patients by L-arginine. Lancet 1991;338:1546–1550.PubMedCrossRefGoogle Scholar
  125. 125.
    Creager MA, Gallagher SJ, Girerd XJ, Coleman SM, Dzau VJ, Cooke JP. L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. J Clin Invest 1992;90:1248–1253.PubMedGoogle Scholar
  126. 126.
    Quyyumi AA, Dakak N, Diodati JG, Gilligan DM, Panza JA, Cannon RO III. Effect of L-arginine on human coronary endothelium-dependent and physiologic vasodilation. J Am Coll Cardiol 1997;30:1220–1227.PubMedCrossRefGoogle Scholar
  127. 127.
    Adams MR, Forsyth CJ, Jessup W, Robinson J, Celermajer DS. Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent vasodilation in healthy young men. J Am Coll Cardiol 1995;26:1054–1061.PubMedCrossRefGoogle Scholar
  128. 128.
    Otsuji S, Nakajima O, Waku S, et al. Attenuation of acetylcholine-induced vasoconstriction by L-arginine is related to the progression of atherosclerosis. Am Heart J 1995;129:1094–1100.PubMedCrossRefGoogle Scholar
  129. 129.
    Thome S, Mullen MJ, Clarkson P, Donald AE, Deanfield JE. Early endothelial dysfunction in adults at risk from atherosclerosis: different responses to L-arginine. J Am Coll Cardiol 1998;32:110–116.CrossRefGoogle Scholar
  130. 130.
    Adams MR, Jessup W, Hailstones D, Celermajer DS. L-arginine reduces human monocyte adhesion to vascular endothelium and endothelial expression of cell adhesion molecules. Circulation 1997;95:662–668.PubMedGoogle Scholar
  131. 131.
    Adams MR, Jessup W, Celermajer DS. Cigarette smoking is associated with increased human monocyte adhesion to endothelial cells: reversibility with oral L-arginine but not vitamin C. J Am Coll Cardiol 1997;29:491–497.PubMedCrossRefGoogle Scholar
  132. 132.
    Aji W, Ravalli S, Szabolcs M, Jiang X-C, Sciacca RR, Michler RE, Cannon PJ. L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL recptor knockout mice. Circulation 1997;95:430–437.PubMedGoogle Scholar
  133. 133.
    Cooke JP, Singer AH, Tsao P, Zera P, Rowan RA, Billingham ME. Anti-atherogenic effects of L-arginine in the hypercholestyerolemic rabbit J Clin Invest 1992;90:1168–1172.PubMedCrossRefGoogle Scholar
  134. 134.
    Wang B-W, Candipan RC, Arjomandi M, Hsiun PT, Tsao PS, Cooke JP. Arginine restores nitric oxide activity and inhibits monocyte accumulation after vascular injury in hypercholesterolemic rabbits. J Am Coll Cardiol 1996;28:1573–1579.PubMedCrossRefGoogle Scholar
  135. 135.
    Hamon M, Vallet B, Bauters C, Wernert N, McFadden EP, LaBlanche J-M, Dupuis B, Bertrand ME. Long-term administration of L-arginine reduces intimai thickening and enhances neoendothelium-dependent acetylcholine relaxation after arterial injury. Circulation 1994;90:1357–1362.PubMedGoogle Scholar
  136. 136.
    Boger RH, Bode-Boger SM, Brandes RP, Phivthong-Ngam L, Bohme M, Nafe R, Mugge A, Frolich J. Dietary L-arginine reduces the progression of atherosclerosis in cholesterol-fed rabbits. Circulation 1997;96:1282–1290.PubMedGoogle Scholar
  137. 137.
    Benzuly KH, Padgett RC, Kaul S, Piegors DJ, Armstrong ML, Heistad DD. Functional improvement precedes structural regression of atherosclerosis. Circulation 1994;89:1810–18.PubMedGoogle Scholar
  138. 138.
    Lerman A, Burnett JC, Higano ST, McKinley LJ, Holmes DR Jr. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation 1998;97:2123–2128.PubMedGoogle Scholar
  139. 139.
    Jeremy RW, McCarron H, Sullivan D. Effects of dietary L-arginine on atherosclerosis and endothelium-dependent vasodilation in the hypercholesterolemic rabbit. Response according to treatment duration, anatomic site, and sex. Circulation 1996;94:498–506.PubMedGoogle Scholar
  140. 140.
    Cayette AJ, Palacino JJ, Cohen RA. Chronic inhibition of nitric oxide production accelerates neointimal formation and impairs endothelial function in hypercholesterolemic rabbits. Arterioscler Thromb 1994; 14:753–59.Google Scholar
  141. 141.
    Naruse K, Shimizu K, Muramatsu M, Toki Y, Miyazaki Y, Okumura K, Takayuki H. Long-term inhibition of NO synthesis promotes atherosclerosis in the hypercholesterolemic rabbit thoracic aorta. PGH2 does not contribute to impaired endothelium-dependent relaxation. Arterioscler Thromb 1994;14:746–752.PubMedGoogle Scholar
  142. 142.
    Jha P, Flather M, Lonn E, et al. The antoxidant vitamins and cardiovascular disease. A critical review of epidemiologic and clinical trial data. Ann Intern Med 1995; 123:860–72.PubMedGoogle Scholar
  143. 143.
    Stephens NG, Parsons A, Schofield P, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996;347:781–86.PubMedCrossRefGoogle Scholar
  144. 144.
    de Longeril M, Salen P, Martin J-L, Mamell N, Monjaud I, Touboul P, Delaye J. Effect of a mediterranean type of diet on the rate of cardiac complications in patients with coronary artery disease. Insights into the cardioprotective effects of certain nutriments. J Am Coll Cardiol 1996;29:1103–1108.Google Scholar
  145. 145.
    .Diaz MN, Frei B, Vita JA, Keaney JF Jr. Antioxidants and heart disease. N Engl J Med 1997;337:408–416PubMedCrossRefGoogle Scholar
  146. 146.
    Mosca L, Rubenfire M, Tarshis T, Tsai A, Pearson T. Clinical predictors of oxidized low-density lipoprotein in patients with coronary artery disease. Am J Cardiol 1997;80:825–830.PubMedCrossRefGoogle Scholar
  147. 147.
    O’Brien KD, Alpers CE, Hokanson JE, Wang S, Chait A/ Oxidation-specific epitopes in human coronary atherosclerosis are not limited to oxidized low-density lipoprotein. Circulation 1996;94:1216–1225.PubMedGoogle Scholar
  148. 148.
    Ohara Y, Peterson TE, Sayegh HS, Subramanian RR, Wilcox JN, Harrison DG. Dietary correction of hypercholesterolemia in the rabbit normalizes endothelial Superoxide anion production. Circulation 1995;92:898–903.PubMedGoogle Scholar
  149. 149.
    Mosca L, Rubenfire M, Mandel C, Rock C, Tarshis T, Tsai A, Pearson T. Antioxidant nutrient supplementation reduces the susceptibility of low density lipoprotein to oxidation in patients with coronary artery disease. J Am Coll Cardiol 1997;30:392–299.PubMedCrossRefGoogle Scholar
  150. 150.
    Jilal I, Grundy SM. Effect of combined supplementation with a-tocopherol, ascorbate, and beta carotene on low-density lipoprotein oxidation. Circulation 1993;88:2780–2786.Google Scholar
  151. 151.
    Levine GN, Frei B, Koulouris SN, et al. Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 1996;93:1107–13.PubMedGoogle Scholar
  152. 152.
    Solzbach U, Hornig B, Jeserich M, Just H. Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation 1997;96:1513–1519.PubMedGoogle Scholar
  153. 153.
    Weber C, Erl W, Weber K, et al. Increased adhesiveness of isolated monocytes to endothelium is prevented by vitamin C intake in smokers. Circulation 1996;93:1488–92.PubMedGoogle Scholar
  154. 154.
    Gilligan DM, Sack MN, Guetta V, et al. Effect of antioxidant vitamins on low density lipoprotein oxidation and impaired endothelium-dependent vasodilation in patients with hypercholesterolemia. J Am Coll Cardiol 1994;24:1611–17.PubMedGoogle Scholar
  155. 155.
    Walldius G, Erikson U, Olsson AG, et al. The effect of probucol on femoral atherosclerosis: the Probucol Quantitative Regression Trial (PQRST). Am J Cardiol 1994;74:875–83.PubMedCrossRefGoogle Scholar
  156. 156.
    John S, Schlaich M, Langenfeld M, Weilprecht H, Schmitz G, Weidinger G, Schmeider RE. Increased bioavailability of nitric oxide after lipid-lowering in hypercholesterolemic patients. Circulation 1998;98:211–216.PubMedGoogle Scholar
  157. 157.
    Minor R Jr, Myers PR, Guerra R Jr, Batas JN, Harrison DG. Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta. J Clin Invest 1990;86:2109–2116.PubMedGoogle Scholar
  158. 158.
    Oemar BS, Tschudi MR, Godoy N, Brovkovich V, Malinski T, Luscher TF. Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis. Circulation 1998;97:2494–2498.PubMedGoogle Scholar
  159. 159.
    Casino PR, Kilcoyne CM, Quyyumi AA, Hoeg JM, Panza JA. Investigation of decreased availability of nitric oxide precursor as the mechanism for impaired endothelium-dependent vasodilation in hypercholesterolemic patients. J Am Coll Cardiol 1994;23:844–850.PubMedGoogle Scholar
  160. 160.
    Chauhan A, More RS, Mullins PA, Taylor GT, Petch MC, Schofield PM. Aging-associated endothelial dysfunction is reversed by L-arginine. J Am Coll Cardiol 1996;28:1796–1804.PubMedCrossRefGoogle Scholar
  161. 161.
    Ohara Y, Pederson TE, Harrison DG. Hypercholesterolemia increases endothelial Superoxide production. J Clin Invest 1993;91:2546–51.PubMedGoogle Scholar
  162. 162.
    Ohara Y, Peterson TE, Sayegh HS, Subramanian RR, Wilcox JN, Harrison DG. Dietary correction of hypercholesterolemia normalizes endothelial Superoxide anion production. Circulation 1995;92:898–903.PubMedGoogle Scholar
  163. 163.
    Garcia CE, Kilcoyne CM, Cardillo C, Cannon RO III, AA, Panza JA. Evidence that endothelial function in patients with hypercholesterolemia is not due to increased extracellular nitric oxide breakdown by Superoxide anions. Am J Cardiol 1995;76:1157–1161.PubMedCrossRefGoogle Scholar
  164. 164.
    Cashin-Hemphill L, Mack WJ, Pogoda JM, et al. Beneficial effects of colestipol-niacin oncoronary atherosclerosis. A 4-year follow-up. JAMA 1990;264:3013–17.PubMedCrossRefGoogle Scholar
  165. 165.
    Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990;323:1289–98.PubMedCrossRefGoogle Scholar
  166. 166.
    Ornish D, Brown SE, Scherwitz, et al. Can lifestyle changes reverse coronary heart disease? The Lefestyle Heart Trial. Lancet 1990;336:129–33.PubMedCrossRefGoogle Scholar
  167. 167.
    Buchwald H, Varco RL, Matts JP, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med 1990;323:946–55.PubMedCrossRefGoogle Scholar
  168. 168.
    The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. N Engl J Med 1997;336:153–162.CrossRefGoogle Scholar
  169. 169.
    Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–89.CrossRefGoogle Scholar
  170. 170.
    Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301–7.PubMedCrossRefGoogle Scholar
  171. 171.
    Sachs FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol. N Engl J Med 1996;335:1001–9.CrossRefGoogle Scholar
  172. 172.
    Downs JR, Clearfield M, Whitney E, Shapiro DR, Beere PA, Langendorfer A, Stein EA, Kruyer W, Gotto AM Jr. Primary prevention of acute coronary events with lovastatin in menand women with average cholesterol levels. Results of AFCAPS/TexCAPS. JAMA 1998;279:1615–1633.PubMedCrossRefGoogle Scholar
  173. 173.
    Fuster V, Steele PM, Chesebro JH. Role of platelets and thrombosis in coronary atherosclerotic disease and sudden death. J Am Coll Cardiol 1986;5:175B–184B.Google Scholar
  174. 174.
    Glagov S, Weisenberg E, Zarins CK, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987;316:1371–75.PubMedCrossRefGoogle Scholar
  175. 175.
    Davies MJ. A macro and micro view of coronary vascular insult in ischemic heart disease. Circulation 1990;82(suppl II);II-38–II-46.Google Scholar
  176. 176.
    Fuster V, Stein B, Ambrose JA, et al. Atherosclerotic plaque rupture and thrombosis-evolving concepts. Circulation 1990;82(suppl II):II-47–II-59.Google Scholar
  177. 177.
    Ip JH, Fuster V, Badimon L, et al. Syndromes of accelerated atherosclerosis: Role of vascular injury and smooth muscle cell proliferation. J Am Coll Cardiol 1990;15:1667–87.PubMedGoogle Scholar
  178. 178.
    Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease. N Engl J Med 1992;326:242–50 and 326;310–18.PubMedCrossRefGoogle Scholar
  179. 179.
    Witstum JL. Role of oxidized low density lipoprotein in atherosclerosis. Br Heart J 1993:69(suppl):S12–S18CrossRefGoogle Scholar
  180. 180.
    Clarkson TB, Pritchard RW, Morgan TM, Remodeling of coronary arteries in human and nonhuman primates. JAMA 1994;271:289–94.PubMedCrossRefGoogle Scholar
  181. 181.
    Libby P. Molecular basis of the acute coronary syndromes. Circulation 1995;91:2844–50.PubMedGoogle Scholar
  182. 182.
    Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995;92:657–71.PubMedGoogle Scholar
  183. 183.
    Grayston JT, Kuo C, Coulson AS, et al. Chlamydia pneumoniae (TWAR) in atherosclerosisof the carotid artery. Circulation 1995;92:3397–3400.PubMedGoogle Scholar
  184. 184.
    Nishioka T, Luo H, Eigler NL, et al. Contribution of inadequate compensatory enlargement to development of human coronary artery stenosis: An in vitro intravascular ultrasound study. J Am Coll Cardiol 1996;27:1571–6.PubMedCrossRefGoogle Scholar
  185. 185.
    Farb A, Burke AP, Tang AL, et al. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996;93:1354–63.PubMedGoogle Scholar
  186. 186.
    Zhou YF, Leon MB, Waclawiw MA, et al. Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy. N Engl J Med 1996;335:624–30.PubMedCrossRefGoogle Scholar
  187. 187.
    Mann JM, Davies MJ. Vulnerable plaque. Relation of characteristics to degree of stenosis in human coronary arteries. Circulation 1996;94:928–31.PubMedGoogle Scholar
  188. 188.
    Burke AP, Farb A, Malcom GT, et al. Coronary risk factors and plaque morphology in menwith coronary disease who die suddenly. N Engl J Med 1997;336:1276–82.PubMedCrossRefGoogle Scholar
  189. 189.
    Ridker PM, Cushman M, Stampfer MJ, et al. Inflamation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973–79.PubMedCrossRefGoogle Scholar
  190. 190.
    Nofer J-R, Tepel M, Kehrel B, et al. low-density lipoproteins inhibit the Na+/H+ antiport inhuman platelets. A novel mechanism enhancing platelet activity in hypercholesterolemia. Circulation 1997;95:1370–77.PubMedGoogle Scholar
  191. 191.
    Hajjar KA, Hamel NM, Harpel PC, Nachman RL. Binding of tissue plaminogen activator to cultured human endothelial cells. J Clin Invest 1987;80:1712–1719.PubMedGoogle Scholar
  192. 192.
    Saksela O, Rifkin DB. Cell-associated plasminogen activation: Regulation and physiological functions. Ann Rev Cell Biol 1988;4:93–126.PubMedGoogle Scholar
  193. 193.
    Hajjar KA, Gavish D, Breslow JL, Nachman RL. Lipoprotein(a) modulation of. endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature 1989;339:303–305.PubMedCrossRefGoogle Scholar
  194. 194.
    Shimokawa H, Aarhus LL, Vanhoutte PM. Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin. Circ Res 1989;64;900–914.PubMedGoogle Scholar
  195. 195.
    Springer TA. Adhesion receptors of the immune system. Nature 1990;346:425–434.PubMedCrossRefGoogle Scholar
  196. 196.
    Hsieh HJ, Li NQ, Frangos JA. Shear stress increases endothelial platelet-derived growth factor mRNA levels. Am J Physiol 1991;260:H642–H646.PubMedGoogle Scholar
  197. 197.
    Tsao PS, Buitrago R, Chan JR, Cooke JP. Fluid flow inhibits endothelial adhesiveness. Nitric oxide and transcriptional regulation of VCAM-1. Circulation 1996;94:1682–1689.PubMedGoogle Scholar
  198. 198.
    Rifkin DB, Moscatelli D. Recent developments in the cell biology of basic fibroblast growth factor. JCellBiol 1989;109:1–6.Google Scholar
  199. 199.
    Battegay EJ, Raines EW, Seifert RA, Bowen-Pope DF, Ross R. TGF-β induces bimodal proliferation of connective tissue cells via complex control of autocrine PDGF loop. Cell 1990;63:515–524.PubMedCrossRefGoogle Scholar
  200. 200.
    Gimbrone MA Jr, Bevilacqua MP, Cubulsky MI. Endothelial-dependent mechanisms of leukocyte adhesion in inflamation and atherosclerosis. Ann N Y Acad Sci 1990;598:77–85.PubMedCrossRefGoogle Scholar
  201. 201.
    Knudsen BS, Nachman RL. Matrix plasminogen activator inhibitor. Modulation of the extracellular proteolytic environment. J Biol Chem 1988;263:9476–9481.PubMedGoogle Scholar
  202. 202.
    Vanhoutte PM, Boulanger CM, Mo JV. Endothelium-derived relaxing factor and converting enzyme inhibition. Am J Cardiol 1995;76:3E–12EPubMedCrossRefGoogle Scholar
  203. 203.
    Tsao PS, Buitrago R, Chan JR, Cooke JP. Fluid flow inhibits endothelial adhesiveness. Nitric oxide and transcriptional regulation of VCAM-1. Circulation 1996;94:1682–1689.PubMedGoogle Scholar
  204. 204.
    Davies PF, Dewey CF, Bussolari SR, Gordon EJ, Gimbrone MA. Influence of hemodynamic forces on vascular endothelial function: In vitro studies of shear stress and pinocytosis in bovine aortic cells. J Clin Invest 1984;73:1121–1129.PubMedGoogle Scholar
  205. 205.
    Sprague PR, Steinbach BC, Nerem RM, Schwartz CJ. Influence of laminar steady-state fluid imposed wall shear stress on the binding, internalization, and degredation of low density lipoprotein by cultured arterial endothelium. Circulation 1987;76:648–656.PubMedGoogle Scholar
  206. 206.
    Davies PF, Dull RO. How does the arterial endothelium sense flow? Hemodynamic forces and signal transduction. Adv Exp Med Biol 1990;273:281–293.PubMedGoogle Scholar
  207. 207.
    Katz SD, Biasucci L, Sabba C, et al. Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure. J Am Coll Cardiol 1992;19:918–25.PubMedGoogle Scholar
  208. 208.
    Luscher TF, Vanhouette PM, Rau L. Antihtpertensive treatment normalizes decreased endothelium-dependent relaxations in rats with salt-induced hypertension. Hypertension 1987; 9(suppl III):III-193–III-197.Google Scholar
  209. 209.
    Panza JA, Casino PR, Kilcoyne CM, et al. Role othelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 1993;87:1468–74.PubMedGoogle Scholar
  210. 210.
    Panza JA, Quyyumi AA, Callahan TS, et al. Effect of antihypertensive treatment on endothelium-dependent vascual relaxation in patients with essential hypertension. J Am CollCardiol 1993;21:1145–51.CrossRefGoogle Scholar
  211. 211.
    Taddei S, Virdis A, Mattei P, et al. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation 1995;91:1981–87.PubMedGoogle Scholar
  212. 212.
    Liberman EH, Gerhard MD, Uehata A, et al. Estrogen improves endothelium-dependent, flow-mediated vasodilation in post menopausal women. Ann Intern Med 1994:121:936–41.Google Scholar
  213. 213.
    Gilligan DM, Badar DM, Panza JA, et al. Acute vascular effects of estrogen in postmenopausal women. Circulation 1994;90:786–91.PubMedGoogle Scholar
  214. 214.
    Reis SE, Gloth ST, Blumenthal RS, et al. Ethinyl estradiol acutely attenuates abnormal coronary vasomotor responses to acetylcholine in postmenopausal women. Circulation 1994;89:52–60.PubMedGoogle Scholar
  215. 215.
    Collins P, Rosano GMC, Sarrel PM, et al. 17B-estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not in men with coronary heart disease. Circulation 1995;92:24–30.PubMedGoogle Scholar
  216. 216.
    McCrohon JA, Walters WAW, Robinson JTC, McCredie RJ, Turner L, Adams MA, Handelsman DJ, Celermajer DS. Arterial reactivity is enhanced in genetic males taking highdose estrogen. J Am Coll Cardiol 1997;29:1432–1436.PubMedCrossRefGoogle Scholar
  217. 217.
    New G, Timmins KL, Duty SJ, Tran BT, O’Brien RC, Harper RW, Meredith IT. Long-term therapy improves vascular function in male to female transsexuals. J Am Coll Cardiol 1997;29:1437–1444.PubMedCrossRefGoogle Scholar
  218. 218.
    Johnstone MT, Creager SJ, Scales KM, et al. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation 1993;88:2510–16.PubMedGoogle Scholar
  219. 219.
    Kushi LH, Folsom AR, Prineas RJ, et al. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med 1996;334:1156–62PubMedCrossRefGoogle Scholar
  220. 220.
    Rim EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the rsk of coronary heart disease in men. N Engl J Med 1993;328:1450–66.CrossRefGoogle Scholar
  221. 221.
    Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993;328:1444–49.PubMedCrossRefGoogle Scholar
  222. 222.
    Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. NEngl J Med 1994;330:1029–35CrossRefGoogle Scholar
  223. 223.
    Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996;334:1145–9PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Robert A. Vogel
    • 1
  1. 1.University of Maryland School of MedicineUSA

Personalised recommendations