Skip to main content
SpringerLink
Log in

Nitric Oxide, Atherosclerosis and the Clinical Relevance of Endothelial Dysfunction

  • Chapter
The Role of Nitric Oxide in Heart Failure

Abstract

The endothelium plays a key role in vascular homeostasis through the release of a variety of autocrine and paracrine substances, the best characterized being nitric oxide. A healthy endothelium acts to prevent atherosclerosis development and its complications through a complex and favorable effect on vasomotion, platelet and leukocyte adhesion and plaque stabilization. The assessment of endothelial function in humans has generally involved the description of vasomotor responses, but more widely includes physiological, biochemical and genetic markers that characterize the interaction of the endothelium with platelets, leukocytes and the coagulation system. Stable markers of inflammation such as high sensitivity C-reactive protein are indirect and potentially useful measures of endothelial function for example.

Attenuation of the effect of nitric oxide accounts for the majority of what is described as endothelial dysfunction. This occurs in response to atherosclerosis or its risk factors. Much remains to be learned about the molecular and genetic pathophysiological mechanisms of endothelial cell abnormalities. However, pharmacological intervention with a growing list of medications can favorably modify endothelial function, paralleling beneficial effects on cardiovascular morbidity and mortality. In addition, several small studies have provided tantalizing evidence that measures of endothelial health might provide prognostic information about an individual patient’s risk of subsequent events. As such, the sum of this evidence makes the clinical assessment of endothelial function an attractive surrogate marker of atherosclerosis disease activity. The review will focus on the role of nitric oxide in atherosclerosis and the clinical relevance of these findings.

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 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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.

Similar content being viewed by others

References

  1. Bunting S, Gryglewski RJ, Moncada S, Vane JS. Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac arteries and inhibits its platelet aggregation. Prostaglandins 1976;12:897–913.

    Article  CAS  PubMed  Google Scholar 

  2. Furchgott RF, Zawadski JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373–376.

    Article  CAS  PubMed  Google Scholar 

  3. Altschul R. Endothelium. New York: The MacMillan Company, 1954, pp. 1–155.

    Google Scholar 

  4. 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;340:1111–1115.

    Article  CAS  PubMed  Google Scholar 

  5. 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;86:228–234.

    CAS  PubMed  Google Scholar 

  6. 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;315:1046–1051.

    CAS  PubMed  Google Scholar 

  7. Zeiher AM, Drexler H, Wollschlaeger H, Just H. Endothelial dysfunction of the coronary microvasculature is associated with impaired coronary blood flow regulation in patients with early atherosclerosis. Circulation 1991;84:1984–1992.

    CAS  PubMed  Google Scholar 

  8. Anderson TJ. Assessment and treatment of endothelial dysfunction in humans. J Am Coll Cardiol 1999;34:631–638.

    CAS  PubMed  Google Scholar 

  9. Farouque HM, Meredith IT. The assessment of endothelial function in humans. Coron Artery Dis 2001;12:445–454.

    Article  CAS  PubMed  Google Scholar 

  10. Diodati JG, Dakak N, Gilligan DM, Quyyumi AA. Effect of atherosclerosis on endothelium-dependent inhibition of platelet activation in humans. Circulation 1998;98:17–24.

    CAS  PubMed  Google Scholar 

  11. Lacoste L, Lam JYT, Hung J, Letchacovski G, Solymoss CB, Waters D. Hyperlipidemia and coronary disease: Correction of the increased thombogenic potential with cholesterol reduction. Circulation 1995;92:3172–3177.

    CAS  PubMed  Google Scholar 

  12. Mickelson JK, Ali MN, Kleiman NS, Lakkis NM, Chow TC, Hughes BJ, Smith CW. Chimeric 7E3 Fab (Reopro) decreases detectabnle CD11b on neutrophils from patients undergoing coronary angioplasty. J Am Coll Cardiol 1999;33:97–106.

    Article  CAS  PubMed  Google Scholar 

  13. Gawaz M, Neumann FJ, Ott I, May A, Schomig A. Platelet activation and coronary stent implantation: Effect of antithrombotic therapy. Circulation 1996;94:279–285.

    CAS  PubMed  Google Scholar 

  14. Gawaz M, Neumann FJ, Schomig A. Evaluation of platelet membrane glycoproteins in coronary artery disease. Circulation 1999;99:e1–e11.

    PubMed  Google Scholar 

  15. Mickelson JK, Lakkis NM, Villarreal-Levy G, Hughes BJ, Smith CW. Leukocyte activation with platelet adhesion after coronary angioplasty: A mechanism for recurrent disease? J Am Coll Cardiol 1996;28:345–353.

    Article  CAS  PubMed  Google Scholar 

  16. Boulanger CM, Scoazec A, Ebrahimian T, Henry P, Mathieu E, Tedgui A, Mallat Z. Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction. Circulation 2001;104:2649–2652.

    CAS  PubMed  Google Scholar 

  17. Davi G, Romano M, Mezzetti A, Procopio A, Iacobelli S, Antiodormi T, Bucciarelli T, Alessandrini P, Cuccurullo F, Bittolo Bon G. Increased levels of soluble P-selectin in hypercholesterolemic patients. Circulation 1998;97:953–957.

    CAS  PubMed  Google Scholar 

  18. Sampietro T, Tuoni M, Ferdeghini M, Ciardi A, Marraccini P, Prontera C, Sassi G, Taddei M, Bionda A. Plasma cholesterol regulates soluble cell adhesion molecule expression in familial hypercholesterolemia. Circulation 1997;96:1381–1385.

    CAS  PubMed  Google Scholar 

  19. Siminiak T, Dye JF, Egdell RM, More R, Wysocki H, Sheridan DJ. The release of soluble adhesion molecules ICAM-1 and E-selectin after acute myocardial infarction and following coronary angioplasty. International Journal of Cardiology 1997;61:113–118.

    Article  CAS  PubMed  Google Scholar 

  20. Smith CW. Potential significance of circulating E-selectin [editorial; comment]. Circulation 1997;95:1986–1988.

    CAS  PubMed  Google Scholar 

  21. Ridker PM, Hennekens C, Roitman-Johnson B, Stampfer MJ, Allen J. Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet 1998;351:88–92.

    Article  CAS  PubMed  Google Scholar 

  22. Ridker PM, Buring JE, Rifai N. Soluble P-selectin and the risk of future cardiovascular events. Circulation 2001;103:491–495.

    CAS  PubMed  Google Scholar 

  23. Biasucci LM, Liuzzo G, Grillo RL, Caligiuri G, Rebuzzi AG, Buffon A, Summaria F, Ginnetti F, Fadda G, Maseri A. Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation 1999;99:855–860.

    CAS  PubMed  Google Scholar 

  24. Buffon A, Liuzzo G, Biasucci LM, Pasqualetti P, Ramazzotti V, Rebuzzi AG, Crea F, Maseri A. Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty. J Am Coll Cardiol 1999;34:1512–1521.

    Article  CAS  PubMed  Google Scholar 

  25. Liuzzo G, Biasucci LM, Gallimore JR, Caligiuri G, Buffon A, Rebuzzi AG, Pepys MB, Maseri A. Enhanced inflammatory response in patients with preinfarction unstable angina. J Am Coll Cardiol 1999;34:1696–1703.

    Article  CAS  PubMed  Google Scholar 

  26. Liuzzo G, Buffon A, Biasucci LM, Gallimore JR, Caligiuri G, Vitelli A, Altamura S, Ciliberto G, Rebuzzi AG, Crea F, Pepys MB, Maseri A. Enhanced inflamatory response to coronary angioplasty in patients with severe unstable angina. Circulation 1998;98:2370–2376.

    CAS  PubMed  Google Scholar 

  27. Ridker PM, Cushman M, Stampfer MJ, Tracy R, Hennekens C. Plasma concentration of C-reactive protein and risks of developing peripheral vascular disease. Circulation 1997;97:425–428.

    Google Scholar 

  28. Ferreiros ER, Boissonnet CP, Pizarro R, Merletti PF, Corrado G, Cagide A, Bazzino OO. Independent prognostic value of elevated C-reactive protein in unstable angina. Circulation 1999;100:1958–1963.

    CAS  PubMed  Google Scholar 

  29. Koenig W, Sund M, Frohlich M, Fischer HG, Lowel H, Doring A, Hutchinson WL, Pepys MB. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: Results from the MONICA (Monitoring trends and determinants in cardiovascular disease) augsburg cohort study, 1984 to 1992 [In Process Citation]. Circulation 1999;99:237–242.

    CAS  PubMed  Google Scholar 

  30. Morrow DA, Rifai N, Antman EM, Weiner DL, McCabe CH, Cannon CP, Braunwald E. C-reactive protein is a potent predictor of mortality independently of an in combination with troponin T in acute coronary syndromes: A TIMI 11A Substudy. J Am Coll Cardiol 1998;31:1460–1465.

    Article  CAS  PubMed  Google Scholar 

  31. Ridker PM, Glynn RJ, Hennekens C. C-reactive protein addes to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 1998;97:2007–2011.

    CAS  PubMed  Google Scholar 

  32. Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, Braunwald E, for the CARE Investigators. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Circulation 1998;98:839–844.

    CAS  PubMed  Google Scholar 

  33. Ridker PM, Hennekens CH, Rifai N, Buring JE, Manson JE. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation 1999;100:713–716.

    CAS  PubMed  Google Scholar 

  34. Roivainen M, Viik-Kajander M, Palosuo T, Toivanen P, Leinonen M, Saikku P, Tenkanen L, Manninen V, Hovi T, ntt. Infections, inflammation, and the risk of coronary heart disease. Circulation 2000; 101:252–257.

    CAS  PubMed  Google Scholar 

  35. Eda S, Kaufmann J, Roos W, Pohl S. Development of a new microparticle-enhanced turbidimetric assay for C-reactive protein with superior features in analytical sensitivity and dynamic range. J Clin Lab Anal 1998;12:137–144.

    Article  CAS  PubMed  Google Scholar 

  36. Verma S, Li SH, Badiwala MV, Weisel RD, Fedak PWM, Li RK, Dhillon B, Mickle DAG. Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein. Circulation 2002;105:1890–1896.

    CAS  PubMed  Google Scholar 

  37. Yeh ETH, Anderson HV, Pasceri V, Willerson JT. C-reactive protein: Linking inflammation to cardiovascular complications. Circulation 2001;104:974–975.

    CAS  PubMed  Google Scholar 

  38. Brown NJ, Gainer JV, Murphey LJ, Vaughan DE. Bradykinin stimulates tissue plasminogen activator release from human forearm vasculature through B2 receptor-dependent, NO synthase-independent, and cyclooxygenase-independent pathway. Circulation 2000;102:2190–2196.

    CAS  PubMed  Google Scholar 

  39. Vaughan DE, Lazos SA, Tong K. Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. A potential link between the renin-angiotensin system and thrombosis. Journal of Clinical Investigation 1995;95:995–1001.

    CAS  PubMed  Google Scholar 

  40. Vaughan DE. The renin-angiotensin system and fibrinolysis. [Review] [29 refs]. American Journal of Cardiology 1997;79:12–16.

    Article  CAS  PubMed  Google Scholar 

  41. Cohen RA, Vanhoutte PM. Endothelium-dependent hyperpolarization: Beyond nitric oxide and cyclic GMP. Circulation 1995;92:3337–3349.

    CAS  PubMed  Google Scholar 

  42. Hui D, Waldron GJ, Galipeau D, Cole WC, Triggle CR. NO/PGIx-independent vasorelaxation and the cytochrome P450 pathway in rabbit carotid artery. British Journal of Pharmacology 1997;120:695–701.

    Google Scholar 

  43. Duffy SJ, Castle SF, Harper RW, Meredith IT. Contribution of vasodilator prostanoids and nitric oxide to resting flow, metabolic vasodilation, and flow-mediated dilation in human coronary circulation. Circulation 1999;100:1951–1957.

    CAS  PubMed  Google Scholar 

  44. Duffy SJ, Tran BT, New G, Tudball RN, Esler MD, Harper RW, Meredith IT. Continuous release of vasodilator prostanoids contributes to regulation of resting forearm blood flow in humans. American Journal of Physiology 1998;274:t–83.

    Google Scholar 

  45. McGuire JJ, Ding H, Triggle CR. Endothelium-derived relaxing factors: A focus on endothelium-derived hyperpolarizing factor(s). Can J Physiol Pharmacol 2001;79:443–470.

    Article  CAS  PubMed  Google Scholar 

  46. Halcox JP, Narayanan S, Cramer-Joyce L, Mincemoyer R, Quyyumi AA. Characterization of endothelium-derived hyperpolarizing factor in the human forearm microcirculation. Am J Physiol Heart Circ Physiol 2001;280:H2470–H2477.

    CAS  PubMed  Google Scholar 

  47. Duncker DJ, Van Zon NS, Altman JD, Pavek TJ, Bache RJ. Role of K+ATP channels in coronary vasodilation during exercise. Circulation 1993;88:1245–1253.

    CAS  PubMed  Google Scholar 

  48. Duncker DJ, Van Zon NS, Ishibashi Y, Bache RJ. Role K +ATP of channels and adenosine in the regulation of coronary blood flow during exercise with normal and restricted coronary blood flow. J Clin Invest 1996;97:996–1009.

    CAS  PubMed  Google Scholar 

  49. Farouque HM, Worthley SG, Meredith IT, Skyrme-Jones RA, Zhang MJ. Effect of ATP-sensitive potassium channel inhibition on resting coronary vascular responses in humans. Circ Res 2002;90:231–236.

    Article  CAS  PubMed  Google Scholar 

  50. Yanagisawa M, Kurihara H, Kimura A, Tomobe Y, Kabayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988;332:411–415.

    Article  CAS  PubMed  Google Scholar 

  51. Haynes WG, Ferro CJ, O’Kane KPJ, Somerville D, Lomax CC, Webb DJ. Systemic endothelin receptor blockade decreases peripheral vascular resistance and blood pressure in humans. Circulation 1996;93:1860–1870.

    CAS  PubMed  Google Scholar 

  52. Richard V, Hogie M, Clozel M, Loffler B-M, Thuillez C. In vivo evidence of an endothelin-induced vasopressor tone after inhibition of nitric oxide synthesis in rats. Circulation 1995;91:771–775.

    CAS  PubMed  Google Scholar 

  53. Wenzel RR, Fleisch M, Shaw S, Noll G, Kaufmann U, Schmitt R, Jones CR, Clozel M, Meier B, Luscher TF. Hemodynamic and coronary effects of the endothelin antagonist bosentan in patients with coronary artery disease. Circulation 1998;98:2235–2240.

    CAS  PubMed  Google Scholar 

  54. Davenport AP, O’Reilly G, Molenaar P, Maguire JJ, Kuc RE, Sharkey A, Bacon CR, Ferro A. Human endothelin receptors characterized using reverse-transcriptase-polymerase chain reaction, in situ hybridization, and subtype-selective ligands BQ 123 and BQ 3020: Evidence for expression of ETb receptors in human vascular smooth muscle. J Cardiovasc Pharmacol 1993;22(suppl 8):S22–S25.

    CAS  PubMed  Google Scholar 

  55. Tsukahara H, Ende H, Magazine HI, Bahou WF, Goligorsky MS. Molecular and functional characterization of the non-isopeptide-selective ETb receptor in endothelial cells: Receptor coupling to nitric oxide synthase. J Biol Chem 1994;269:21778–21785.

    CAS  PubMed  Google Scholar 

  56. Kinlay S, Behrendt D, Wainstein M, Beltrame J, Fang JC, Creager MA, Selwyn AP, Ganz P. Role of endothelin-1 in the active constriction of human atherosclerotic coronary arteries. Circulation 2001;104:1114–1118.

    CAS  PubMed  Google Scholar 

  57. Dzau VJ, Burt DW, Pratt RE. Molecular biology to the renin-angiotensin system. American Journal of Physiology 1988;255:F563–F573.

    CAS  PubMed  Google Scholar 

  58. Dzau VJ, Re R. Tissue angiotensin system in cardiovascular medicine: A paradigm shift. Circulation 1994;89:493–498.

    CAS  PubMed  Google Scholar 

  59. 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.

    CAS  PubMed  Google Scholar 

  60. Golino P, Piscione F, Willerson JT, Cappelli-Bigazzi M, Focaccio A, Villari B, Indolfi C, Russolillo E, Condorelli M, Chiariello M. Divergent effects of serotonin on coronary artery dimensions and blood flow in patients with coronary atherosclerosis and control patients. N Engl J Med 1991;324:641–648.

    CAS  PubMed  Google Scholar 

  61. Zeiher AM, Drexler H, Wollschlager H, Just H. Modulation of coronary vasomotor tone in humans: Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 1991;83:391–401.

    CAS  PubMed  Google Scholar 

  62. Quyyumi AA, Dakak N, Andrews NP, Hussain S, Arora S, Gilligan DM, Panza JA, Cannon RO3. Nitric oxide activity in the human coronary circulation. J Clin Invest 1995;95:1747–1755.

    CAS  PubMed  Google Scholar 

  63. Doucette JW, Corl PD, Payne HM, Flynn AE, Goto M, Nassi M, Segal J. Validation of a doppler guide wire for intravascular measurement of coronary artery flow velocity. Circulation 1992;85:1899–1911.

    CAS  PubMed  Google Scholar 

  64. Uren NG, Marraccini P, Gistri R, de Silva R, Camici PG. Altered coronary vasodilator reserve and metabolism in myocardium subtended by normal arteries in patients with coronary artery disease. Journal of the American College of Cardiology 1993;22:650–658.

    CAS  PubMed  Google Scholar 

  65. Vallance P, Collier JG, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 1989;160:881–886.

    Google Scholar 

  66. Goodhart DM, Anderson TJ. Coronary arterial vasomotion: The role of nitric oxide and the influence of coronary atherosclerosis and its risks. Am J Cardiol 1998;82:1034–1039.

    Article  CAS  PubMed  Google Scholar 

  67. Quyyumi AA, Dakak N, Andrews NP, Gilligan DM, Panza JA, Cannon RO3. Contribution of nitric oxide to metabolic coronary vasodilation in the human heart. Circulation 1995;92:320–326.

    CAS  PubMed  Google Scholar 

  68. Ross R. The pathogenesis of atherosclerosis: A perspective for the 1990’s. Nature 1993;362:801–809.

    Article  CAS  PubMed  Google Scholar 

  69. Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001;104:365–372.

    CAS  PubMed  Google Scholar 

  70. Meredith IT, Anderson TJ, Uehata A, Yeung AC, Selwyn AP, Ganz P. Role of endothelium in ischemic coronary syndromes. [Review]. American Journal of Cardiology 1993;72:27C–31C; discussion 31C.

    Article  CAS  PubMed  Google Scholar 

  71. Egashira K, Inou T, Hirooka Y, Yamada A, Maruoka Y, Kai H, Sugimachi M, Suzuki S, Takeshita A. Impaired coronary blood flow response to acetylcholine inpatients with coronary risk factors and proximal atherosclerotic lesions. J Clin Invest 1993;91:29–37.

    CAS  PubMed  Google Scholar 

  72. Prasad A, Narayanan S, Waclawiw MA, Epstein N, Quyyumi AA. The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity. J Am Coll Cardiol 2000;36:1579–1586.

    CAS  PubMed  Google Scholar 

  73. Quyyumi AA, Dakak N, Mulcahy D, Andrews NP, Husain S, Panza JA, Cannon RO3. Nitric oxide activity in the atherosclerotic human coronary circulation. J Am Coll Cardiol 1997;29:308–317.

    CAS  PubMed  Google Scholar 

  74. Anderson TJ, Gerhard MD, Meredith IT, Charbonneau F, Delagrange D, Creager MA, Selwyn AP, Ganz P. Systemic nature of endothelial dysfunction in atherosclerosis. [Review]. American Journal of Cardiology 1995;75:71B–74B.

    Article  CAS  PubMed  Google Scholar 

  75. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995;26:1235–1241.

    CAS  PubMed  Google Scholar 

  76. Williams SB, Cusco JA, Roddy M-A, Johnstone M, Creager MA. Impaired nitric oxide-mediated vasodilation in humans with non-insulin-dependent diabetes mellitus. JACC 1996;27:567–574.

    CAS  PubMed  Google Scholar 

  77. Vallance P. Use of L-arginine and its analogs to study nitric oxide pathway in humans. Methods Enzymol 1996;269:453–459.

    CAS  PubMed  Google Scholar 

  78. Mullen MJ, Kharbanda RK, Cross J, Donald AE, Taylor M, Vallance P, Deanfield JE, MacAllister RJ. Heterogenous nature of flow-mediated dilatation in human conduit arteries in vivo: Relevance to endothelial dysfunction in hypercholesterolemia. Circ Res 2001;88:145–151.

    CAS  PubMed  Google Scholar 

  79. Andrews NP, Husain M, Dakak N, Quyyumi AA. Platelet inhibitory effect of nitric oxide in the human coronary circulation: Impact of endothelial dysfunction. J Am Coll Cardiol 2001;37:510–516.

    CAS  PubMed  Google Scholar 

  80. Freedman JE, Ting B, Hankin B, Loscalzo J, Keaney JFJ, Vita JA. Impaired platelet production of nitric oxide predicts presence of acute coronary syndromes [In process citation]. Circulation 1998;98:1481–1486.

    CAS  PubMed  Google Scholar 

  81. Freedman JE, Loscalzo J. Platelet-monocyte aggregates: Bridging thrombosis and inflammation. Circulation 2002;105:2130–2132.

    Article  PubMed  Google Scholar 

  82. Kubes P, Suzuki M, Granger DN. Nitric oxide: An endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 1991;88:4651–4655.

    CAS  PubMed  Google Scholar 

  83. Kubes P. Polymorphonuclear leukocyte-endothelium interactions: A role for pro-inflammatory and anti-inflammatory molecules. Can J Physiol Pharmacol 1995;71:88–97.

    Google Scholar 

  84. Fischell TA, Bausback KN, McDonald TV. Evidence for altered epicardial coronary artery autoregulation as a cause of distal coronary vasoconstriction after successful percutaneous transluminal coronary angioplasty. J Clin Invest 1990;86:575–584.

    CAS  PubMed  Google Scholar 

  85. Gregorini L, Fajadet J, Robert G, Cassagneau B, Bernis M, Marco J. Coronary vasoconstriction after percutaneous transluminal coronary angioplasty is attenuated by anti-adrenergic drugs. Circulation 1994;90:895–907.

    CAS  PubMed  Google Scholar 

  86. Gregorini L, Marco J, Palombo C, Kozakova M, Anguissola JB, Cassagneau B, Bernies M, Distante A, Marco I, Fajadet J, Zanchetti A. Postischemic left ventricular dysfunction is abolished by alpha-adrenergic blocking agents. J Am Coll Cardiol 1998;31:992–1001.

    Article  CAS  PubMed  Google Scholar 

  87. Rodriguez A, Santaera O, Larribau M, Fernandez M, Sarmiento R, Perez Balino N, Newell JB, Roubin G, Palacios IF. Coronary stenting decreases restenosis in lesions with early loss in luminal diameter 24 hours after successful PTCA. Circulation 1995;91:1397–1402.

    CAS  PubMed  Google Scholar 

  88. Caramori PRA, Lima VC, Seidelin PH, Newton GE, Parker JD, Adelman AG. Long-term endothelial dysfunction after coronary artery stenting. J Am Coll Cardiol 1999;34:1675–1679.

    Article  CAS  PubMed  Google Scholar 

  89. Aymong ED, Curtis MJ, Youssef M, Graham MM, Shewchuk L, Leschuk W, Anderson TJ. Abciximab attenuates coronary microvascular endothelial dysfunction following coronary stenting. Circulation 2002 (In press).

    Google Scholar 

  90. Merhi Y, Guidoin R, Provost P, Leung TK, Lam JY. Increase of neutrophil adhesion and vasoconstriction with platelet deposition after deep arterial injury by angioplasty. American Heart Journal 1995;129:445–451.

    Article  CAS  PubMed  Google Scholar 

  91. Serrano CVJ, Ramires JA, Venturinelli M, Arie S, D’Amico E, Zweier JL, Pileggi F, da Luz PL. Coronary angioplasty results in leukocyte and platelet activation with adhesion molecule expression. Evidence of inflammatory responses in coronary angioplasty. Journal of the American College of Cardiology 1997;29:1276–1283.

    CAS  PubMed  Google Scholar 

  92. van Beusekom HMM, Whelan DM, Hofma SH, Krabbendam SC, van Hinsbergh VWM, Verdouw PD, van der Giessen WJ. Long-term endothelial dysfunction is more pronounced after stenting than after balloon angioplasty in porcine coronary arteries. J Am Coll Cardiol 1998;32:1109–1117.

    PubMed  Google Scholar 

  93. Merhi Y, Provost P, Guidoin R, Latour JG. Importance of platelets in neutrophil adhesion and vasoconstriction after deep carotid arterial injury by angioplasty in pigs. Arterioscler Thromb Vasc Biol 1997;17:1185–1191.

    CAS  PubMed  Google Scholar 

  94. Jang Y, Lincoff MA, Plow EF, Topol EJ. Cell adhesion molecules in coronary artery disease. J Am Coll Cardiol 1994.

    Google Scholar 

  95. Topol EJ, Serruys PW. Frontiers in interventional cardiology. Circulation 1998;98:1802–1820.

    CAS  PubMed  Google Scholar 

  96. Belch JJ, Shaw JW, Kirk G, McLaren M, Robb R, Maple C, Morse P. The white blood cell adhesion molecule Eselectin predicts restenosis in patients with intermittent claudication undergoing percutaneous transluminal angioplasty [see comments]. Circulation 1997;95:2027–2031.

    CAS  PubMed  Google Scholar 

  97. Inoue T, Sakai Y, Fujito T, Hoshi K, Hayashi T, Takayanagi K, Morooka S. Clinical significance of neutrophil adhesion molecules expression after coronary angioplasty on the development of restenosis. Thrombosis and Haemostasis 1998;79:54–58.

    CAS  PubMed  Google Scholar 

  98. Tschoepe D, Schultheib MD, Kolarov P, Schwippert B, Dannehl K, Volksw D, Nieuwenhuis HK, Kehrel B, Strauer B, Gries FA. Platelet membrane activation markers are predictive for increased risk of acute ischemic events after PTCA. Circulation 1993;88:37–42.

    CAS  PubMed  Google Scholar 

  99. Heeschen C, Hamm CW, Bruemmer J, Simoons ML, for the CAPTURE Investigator. Predictive value of Creactive protein and troponin T in patients with unstable angina: A comparative analysis. J Am Coll Cardiol 2000;35:1535–1542.

    Article  CAS  PubMed  Google Scholar 

  100. Mueller C, Buettner HJ, Hodgson JM, Marsch S, Perruchoud AP, Roskamm H, Neumann FJ. Inflammation and long-term mortality after non-ST elevation acute coronary syndrome treated with a very early invasive strategy in 1042 consecutive patients. Circulation 2002;105:1412–1415.

    PubMed  Google Scholar 

  101. Rubanyi GM, Vanhoutte PM. Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. American Journal of Physiology 1986;250:H822–H827.

    CAS  PubMed  Google Scholar 

  102. Oemar BS, Tschudi MR, Godoy N, Brovkovich V, Malinkski T, Luscher T. Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis. Circulation 1998;97:2494–2498.

    CAS  PubMed  Google Scholar 

  103. 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.

    CAS  Google Scholar 

  104. Stroes ES, Hijmering M, Zandvoort M, Rabelink TJ, Faassen EE. Origin of superoxide production by nitric oxide synthase. FEBS Lett 1998;438:161–164.

    Article  CAS  PubMed  Google Scholar 

  105. Verhaar MC, Stroes E, Rabelink TJ. Folates and cardiovascular disease. Arterioscler Thromb Vase Biol 2002;22:6–13.

    CAS  Google Scholar 

  106. Wever RMF, LĂ¼scher TF, Cosentino F, Rabelink T. Atherosclerosis and the two faces of endothelial nitric oxide synthase. Circulation 1998;97:108–112.

    CAS  PubMed  Google Scholar 

  107. Michel T, Feron O. Nitric oxide synthases: Which, where, how and why? J Clin Invest 1997;100:2146–2152.

    CAS  PubMed  Google Scholar 

  108. Thony B, Auerbach G, Blau N. Tetrahydrobiopterin biosynthesis, regeneration and function. Biochemical Journal 2000;347:1–16.

    CAS  PubMed  Google Scholar 

  109. Cosentino F, Katusic ZS. Tetrahydrobiopterin and dysfunction of endothelial nitric oxide synthase in coronary arteries. Circulation 1995;91:139–144.

    CAS  PubMed  Google Scholar 

  110. Heinzel B, John M, Klatt P, Bohme E, Meyer B. Ca2+/calmodulin-depdnent formation of hydrogen peroxide by brain nitric oxide synthase. Biochem J 1992;281:627–630.

    CAS  PubMed  Google Scholar 

  111. Pritchard KA, Jr., Groszek L, Smalley DM, Sessa WC, Wu M, Villalon P, Wolin MS, Stemerman MB. Native low-density lipoprotein increases endothelial cell nitric oxide synthase generation of superoxide anion. Circ Res 1995;77:510–518.

    CAS  PubMed  Google Scholar 

  112. Vasquez-Vivar J, Kalyanaraman B, Martasek P, Hogg N, Masters BS, Karoui H, Tordo P, Pritchard KAJ. Superoxide generation by endothelial nitric oxide synthase: The influence of cofactors. Proc Natl Acad Sci USA 2000;95:9220–9225.

    Google Scholar 

  113. Wermer ER, Werner-Felmayer G, Wachter H, Mayer B. Biosynthesis of nitric oxide: Dependence of pteridine metabolism. Rev Physiol Biochem Pharmacol 1995;127:97–135.

    Google Scholar 

  114. Huang A, Vita JA, Venema RC, Keaney J. Ascorbic acid enhances endothelial nitric oxide synthase activity by increasing intracellular tetrahydrobiopterin. J Biol Chem 2000.

    Google Scholar 

  115. Shinozaki K, Kashiwagi A, Nishio Y, Okamura T, Yoshida Y, Masada M, Toda N, Kikkawa R. Abnormal biopterin metabolism is a major cause of impaired endothelium-dependent relaxation through nitric oxide/O −2 imbalance in insulin-resitant rat aorta. Diabetes 1999;48:2437–2445.

    CAS  PubMed  Google Scholar 

  116. Shinozaki K, Nishio Y, Okamura T, Yoshida Y, Maegawa H, Kojima H, Masada M, Toda N, Kikkawa R, Kashiwagi A. Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and vascular oxidative stress in the aortas of insulin-resistant rats. Circ Res 2000;87:566–573.

    CAS  PubMed  Google Scholar 

  117. Heller R, Unbehaun A, Schellenberg B, Mayer B, Werner-Felmayer G, Wermer ER. L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin. Journal of Biological Chemistry 2001;276:40–47.

    Article  CAS  PubMed  Google Scholar 

  118. Verhaar MC, Wever RM, Kastelein JJ, van Loon D, Milstien S, Koomans HA, Rabelink TJ. Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. A randomized placebo-controlled trial. Circulation 1999;100:335–338.

    CAS  PubMed  Google Scholar 

  119. Wilmink HW, Stroes ES, Erkelens WD, Gerritsen WB, Wever R, Banga JD, Rabelink TJ. Influence of folic acid on postprandial endothelial dysfunction. Arterioscler Thromb Vasc Biol 2000;20:185–188.

    CAS  PubMed  Google Scholar 

  120. Hyndman ME, Verma S, Rosenfeld RJ, Anderson TJ, Parsons HG. Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function. Am J Physiol Heart Circ Physiol 2002;282:H2167–H2172.

    CAS  PubMed  Google Scholar 

  121. Stroes ES, van Faassen EE, Yo M, Martasek P, Boer P, Govers R, Rabelink TJ. Folic acid reverts dysfunction of endothelial nitric oxide synthase. Circ Res 2000;86:1129–1134.

    CAS  PubMed  Google Scholar 

  122. Yoshimura M, Yasue H, Nakayama M, Shimasaki Y, Sumida H, Sugiyama S, Kugiyama K, Ogawa H, Ogawa Y, Saito Y, Miyamoto Y, Nakao K. A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese. Human Genetics 1998;103:65–69.

    Article  CAS  PubMed  Google Scholar 

  123. Hyndman ME, Parsons HG, Verma S, Bridge PJ, Edworthy S, Jones C, Lonn E, Charbonneau F, Anderson TJ. The T-786->C mutation in endothelial nitric oxide synthase is associated with hypertension. Hypertension 2002;39:919–922.

    Article  CAS  PubMed  Google Scholar 

  124. Steinberg D. Antioxidants and atherosclerosis: A current assessment. Circulation 1991;84:1420–1425.

    CAS  PubMed  Google Scholar 

  125. Kugiyama K, Kerns SA, Morrisett JD, Roberts R, Henry PD. Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Nature 1990;344:160–162.

    Article  CAS  PubMed  Google Scholar 

  126. Kugiyama K, Ohgushi M, Sugiyama S, Murohara T, Fukunaga K, Miyamtoto E, Yasue H. Lysophosphatidylcholine inhibits surface receptor-mediated intracellular signals in endothelial cells by a pathway involving protein kinase C activation. Circ Res 1992;71:1422–1428.

    CAS  PubMed  Google Scholar 

  127. Ohgushi M, Kugiyama K, Fukunaga K, Murohara T, Sugiyama S, Miyamoto E, Yasue H. Protein kinase C inhibitors prevent impairment of endothelium-dependent relaxation by oxidatively modified LDL. Arteriosclerosis and Thrombosis 1993;13:1525–1532.

    CAS  PubMed  Google Scholar 

  128. Liao JK, Clark SL. Regulation of G-protein alpha i2 subunit expression by oxidized low-density lipoprotein. J Clin Invest 1995;95:1457–1463.

    CAS  PubMed  Google Scholar 

  129. 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;70:1191–1197.

    CAS  PubMed  Google Scholar 

  130. Lerman A, Webster MWI, Chesebro JH, Edwards WD, Wei C-M, Fuster V, Burnett JC, Jr. Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs. Circulation 1993;88:2923–2928.

    CAS  PubMed  Google Scholar 

  131. 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;93:1647–1650.

    CAS  PubMed  Google Scholar 

  132. 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;93:1346–1353.

    CAS  PubMed  Google Scholar 

  133. 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;278:1682–1686.

    Article  CAS  PubMed  Google Scholar 

  134. Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A, Bayazeed B, Baron AD. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation. J Clin Invest 1997;100:1230–1239.

    CAS  PubMed  Google Scholar 

  135. 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.

    CAS  PubMed  Google Scholar 

  136. Barry OP, Pratico D, Savani RC, FitzGerald GA. Modulation of monocyte-endothelial cell interactions by platelet microparticles. J Clin Invest 1998;102:136–144.

    CAS  PubMed  Google Scholar 

  137. Mesri M, Altieri DC. Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem 1999;274:23111–23118.

    Article  CAS  PubMed  Google Scholar 

  138. Ridker PM. High-sensitivity C-reactive protein: Potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001;103:1813–1818.

    CAS  PubMed  Google Scholar 

  139. Pasceri V, Willerson JT, Yeh ETH. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000;102:2165–2168.

    CAS  PubMed  Google Scholar 

  140. Pasceri V, Chang J, Willerson JT, Yeh ETH. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerotic drugs. Circulation 2001;103:2531–2534.

    CAS  PubMed  Google Scholar 

  141. Zwaka TP, Hombach V, Torzewski J. C-reactive protein-mediated low density lipoprotein uptake by macrophages: Implications for atherosclerosis. Circulation 2001;103:1194–1197.

    CAS  PubMed  Google Scholar 

  142. Ohara Y, Peterson TE, Harrison DG. Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 1993;91:2546–2551.

    CAS  Google Scholar 

  143. Ohara Y, Peterson TE, Zheng B, Kuo JF, Harrison DG. Lysophosphatidylcholine increases vascular superoxide anion production via protein kinase C activation. Arteriosclerosis and Thrombosis 1994;14:1007–1013.

    CAS  Google Scholar 

  144. 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 [see comments]. New England Journal of Medicine 1995;332:488–493.

    Article  CAS  PubMed  Google Scholar 

  145. Dupuis J, Tardif JC, Cernacek P, Theroux P. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes: The RECIFE (Reduction of cholesterol in ischemia and function of the endothelium) trial. Circulation 1999;99:3227–3233.

    CAS  PubMed  Google Scholar 

  146. Treasure CB, Klein L, Weintraub WS, Talley JD, Stillabower ME, Kosinski AS, 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;332:481–487.

    CAS  PubMed  Google Scholar 

  147. Tamai O, Matsuoka H, Itabe H, Wada Y, Kohno K, Imaizumi T. Single LDL apheresis improves endothelium-dependent vasodilation in hypercholesterolemic humans. Circulation 1997;95:76–82.

    CAS  PubMed  Google Scholar 

  148. Leung WH, Lau CP, Wong CK. Beneficial effect of cholesterol-lowering therapy on coronary endothelium-dependent relaxation in hypercholesterolaemic patients. Lancet 1993;341:1496–1500.

    Article  CAS  PubMed  Google Scholar 

  149. Feron O, Dessy C, Desager JP, Balligand JL. Hydroxymethylglutaryl-coenzyme a reductase inhibition promotes endothelial nitric oxide synthase activation through a decrease in caveolin abundance. Circulation 2001;103:113–118.

    CAS  PubMed  Google Scholar 

  150. Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: Implications for plaque stabilization. Circulation 2001;103:926–933.

    CAS  PubMed  Google Scholar 

  151. Llevadot J, Murasawa S, Kureishi Y, Uchida S, Masuda H, Kawamoto A, Walsh K, Isner JM, Asahara T. HMGCoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells. J Clin Invest 2001;108:399–405.

    Article  CAS  PubMed  Google Scholar 

  152. Freeman DJ, Norrie J, Sattar N, Neely RD, Cobbe SM, Ford I, Isles C, Lorimer AR, Macfarlane PW, McKillop JH, Packard CJ, Shepherd J, Gaw A. Pravastatin and the development of diabetes mellitus: Evidence for a protective treatment effect in the West of Scotland coronary prevention study. Circulation 2001;103:357–362.

    CAS  PubMed  Google Scholar 

  153. Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels. JAMA 2001;286:64–70.

    CAS  PubMed  Google Scholar 

  154. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1999;100:230–235.

    CAS  PubMed  Google Scholar 

  155. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AM, Jr., the Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. The New England Journal of Medicine 2001;344:1959–1965.

    Article  CAS  PubMed  Google Scholar 

  156. Spieker LE, Sudano I, Hurlimann D, Lerch PG, Lang MG, Binggeli C, Corti R, Ruschitzka F, Luscher TF, Noll G. High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation 2002;105:1399–1402.

    CAS  PubMed  Google Scholar 

  157. HOPE Investigators: Effects of an angiotensin-converting-enzyme-inhibitor, Ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145–153.

    Google Scholar 

  158. 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. Contribution to alterations of vasomotor tone. J Clin Invest 1996;97:1916–1923.

    CAS  PubMed  Google Scholar 

  159. Hornig B, Kohler C, Drexler H. Role of bradykinin in mediating vascular effects of angiotensin-converting enzyme inhibitors in humans. Circulation 1997;95:1115–1118.

    CAS  PubMed  Google Scholar 

  160. Antony I, Lerebours G, Nitenberg A. Angiotensin-converting enzyme inhibition restores flow-dependent and cold pressor test-induced dilations in coronary arteries of hypertensive patients. Circulation 1996;94:3115–3122.

    CAS  PubMed  Google Scholar 

  161. Mancini GBJ, Henry GC, Macaya C, O’Neill BJ, Pucillo AL, Carere RG, Wargovich TJ, Mudra H, Luscher TF, Klibaner MI, Haber HE, Uprichard ACG, Pepine CJ, Pitt B. Angiotensin converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease: The TREND study. Circulation 1996;94:258–265.

    CAS  PubMed  Google Scholar 

  162. Anderson TJ, Elstein E, Haber HE, Charbonneau F. Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study). J Am Coll Cardiol 2000;35:60–66.

    CAS  PubMed  Google Scholar 

  163. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861–869.

    Article  CAS  PubMed  Google Scholar 

  164. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol. Lancet 2002;359:995–1003.

    CAS  PubMed  Google Scholar 

  165. Lindholm LH, Ibsen H, Dahlof B, Devereux RB, Beevers G, de Faire U, Fyhrquist F, Julius S, Kjeldsen SE, Kristiansson K, Lederballe-Pedersen O, Nieminen MS, Omvik P, Oparil S, Wedel H, Aurup P, Edelman J, Snapinn S. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol. Lancet 2002;359:1004–1010.

    CAS  PubMed  Google Scholar 

  166. Prasad A, Tupas-Habib T, Schenke WH, Mincemoyer R, Panza JA, Waclawin MA, Ellahham S, Quyyumi AA. Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis. Circulation 2000;101:2349–2354.

    CAS  PubMed  Google Scholar 

  167. Cheetham C, Collis J, O’Driscoll G, Stanton K, Taylor R, Green D. Losartan, an angiotensin type I receptor antagonist, improves endothelial function in non-insulin-dependent diabetes. J Am Coll Cardiol 2000;36:1461–1466.

    Article  CAS  PubMed  Google Scholar 

  168. Cheetham C, O’Driscoll G, Stanton K et al. Losartan, an angiotensin type I receptor antagonist, improves conduit vessel endothelial function in type II diabetes. Clinical Science 2001;100:13–17.

    Article  CAS  PubMed  Google Scholar 

  169. UK Prospective Diabetes Study Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854–865.

    Google Scholar 

  170. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest 1996;97:2601–2610.

    CAS  PubMed  Google Scholar 

  171. Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in diet treated type II diabetes mellitus. J Am Coll Cardiol 2001 (In press).

    Google Scholar 

  172. Verma S, Lovren F, Dumont AS, Mather KJ, Maitland A, Kieser TM, Triggle CR, Anderson TJ. Tetrahydrobiopterin improves endothelial function in human saphenous veins: A novel mechanism. Journal of Thoracic and Cardiovascular Surgery 2000;120:668–671.

    Article  CAS  PubMed  Google Scholar 

  173. Setoguchi S, Mohri M, Shimokawa H, Takeshita A. Tetrahydrobiopterin improves endothelial dysfunction in coronary microcirculation in patients without epicardial coronary artery disease. J Am Coll Cardiol 2001;38:493–498.

    Article  CAS  PubMed  Google Scholar 

  174. Maier W, Cosentino F, Lutolf RB, Fleisch M, Seiler C, Hess OM, Meier B, Luscher TF. Tetrahydrobiopterin improves endothelial function in patients with coronary artery disease. J Cardiovasc Pharmacol 2000;35:173–178.

    Article  CAS  PubMed  Google Scholar 

  175. Stroes E, Kastelein J, Erkelens W, Wever R, Koomans H, Luscher T, Rabelink T. Tetrahydrobiopterin restores endothelial function in hypercholesterolemia. J Clin Invest 1997;99:41–46.

    CAS  PubMed  Google Scholar 

  176. Ueda S, Matsuoka H, Miyazaki H, Usui M, Okuda S, Imaizumi T. Tetrahydrobiopterin restores endotheial function in long-term smokers. J Am Coll Cardiol 2000;35:71–75.

    Article  CAS  PubMed  Google Scholar 

  177. Heitzer T, Brockhoff C, Mayer B, Warnholtz A, Mollnau H, Henne S, Meinertz T, Munzel T. Tetrahydrobiopterin improves endothelium-dependent vasodilation in chronic smokers. Circ Res 2000;86:e36–e40.

    CAS  PubMed  Google Scholar 

  178. Heitzer T, Krohn K, Albers S, Meinertz T. Tetrahydrobiopterin improves endothelium-dependent vasodilation by increasing nitric oxide activity in patients with Type II diabetes mellitus. Diabetologia 2000;43:1435–1438.

    Article  CAS  PubMed  Google Scholar 

  179. Bellamy MF, McDowell IF, Ramsey MW, Brownlee M, Bones C, Newcombe RG, Lewis MJ. Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults. Circulation 1998;98:1848–1852.

    CAS  PubMed  Google Scholar 

  180. Bellamy MF, McDowell IF, Ramsey MW, Brownlee M, Newcombe RG, Lewis MJ. Oral folate enhances endothelial function in hyperhomocysteinaemic subjects [see comments]. European Journal of Clinical Investigation 1999;29:659–662.

    Article  CAS  PubMed  Google Scholar 

  181. Chao CL, Chien KL, Lee YT. Effect of short-term vitamin (folic acid, vitamins B6 and B12) administration on endothelial dysfunction induced by post-methionine load hyperhomocysteinemia. American Journal of Cardiology 1999;84:1359–1361.

    Article  CAS  PubMed  Google Scholar 

  182. Title LM, Cummings PM, Giddens K, Genest JJ, Jr., Nassar BA. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2000;36:758–765.

    CAS  PubMed  Google Scholar 

  183. Woo KS, Chook P, Lolin YI, Sanderson JE, Metreweli C, Celermajer DS. Folic acid improves arterial endothelial function in adults with hyperhomocytinemia. J Am Coll Cardiol 1999;34:2002–2006.

    Article  CAS  PubMed  Google Scholar 

  184. Doshi SN, McDowell IF, Moat SJ, Lang D, Newcombe RG, Kredan MB, Lewis MJ, Goodfellow J. Folate improves endothelial function in coronary artery disease: An effect mediated by reduction of intracellular superoxide? Arterioscler Thromb Vasc Biol 2001;21:1196–1202.

    CAS  PubMed  Google Scholar 

  185. Verhaar MC, Wever RMF, Kastelein JJP, van Dam T, Koomans HA, Rabelink TJ. 5-Methyltetrahydrofolate,the active form of folic acid restores endothelial function in familial hypercholesterolemia. Circulation 1998;97:237–241.

    CAS  PubMed  Google Scholar 

  186. Libby P, Simon DI. Inflammation and thrombosis: The clot thickens. Circulation 2001;103:1718–1720.

    CAS  PubMed  Google Scholar 

  187. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105:1135–1143.

    CAS  PubMed  Google Scholar 

  188. Hasdai D, Gibbons RJ, Holmes DR, Jr., Higano ST, Lerman A. Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects. Circulation 1997;96:3390–3395.

    CAS  PubMed  Google Scholar 

  189. Quyyumi AA, Cannon RO3, Panza JA, Diodati JG, Epstein SE. Endothelial dysfunction in patients with chest pain and normal coronary arteries. Circulation 1992;86:1864–1871.

    CAS  PubMed  Google Scholar 

  190. Davis SF, Yeung AC, Meredith IT, Charbonneau F, Ganz P, Selwyn AP, Anderson TJ. Early endothelial dysfunction predicts the development of transplant coronary artery disease at 1 year posttransplant. Circulation 1996;93:457–463.

    CAS  PubMed  Google Scholar 

  191. Schachinger V, Britten MB, Zeiher A. Impaired epicardial coronary vasoreactivity predicts for adverse cardiovascular events during long-term follow-up. Circulation 2000;101:1902–1907.

    Google Scholar 

  192. Suwaidi JA, Hamasaki S, Higano ST, Velianou JL, Araujo NA, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000;101:948–954.

    CAS  PubMed  Google Scholar 

  193. Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, Ferraro A, Chello M, Mastroroberto P, Verdecchia P, Schillaci G. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 2001;104:191–196.

    CAS  PubMed  Google Scholar 

  194. Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001;104:2673–2678.

    CAS  PubMed  Google Scholar 

  195. Neunteufl T, Heher S, Katzenschlager R, Wolfl G, Kostner K, Maurer G, Weidinger F. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol 2000;86:207–210.

    Article  CAS  PubMed  Google Scholar 

  196. Gokce N, Keaney JF, Jr., Hunter LM, Watkins MT, Menzoian JO, Vita JA. Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: A prospective study. Circulation 2002;105:1567–1572.

    Article  PubMed  Google Scholar 

  197. Anderson TJ, Robertson A, Hildebrand K, Conradson HE, Jones C, Bridge P, Edworthy S, Lonn EM, Verma S, Charbonneau F. The FATE of endothelial function testing: Rational and design of the firefighters and their endothelium (FATE) Study. Can J Cardiol 2002 (In press).

    Google Scholar 

  198. Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis. JAMA 2001;285:2481–2485.

    Article  CAS  PubMed  Google Scholar 

  199. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy Men [In process citation]. Circulation 2000;101:1767–1772.

    CAS  PubMed  Google Scholar 

  200. Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E. Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 2000;101:2149–2153.

    CAS  PubMed  Google Scholar 

  201. Ridker PM, Cushman M, Stampfer MJ, Tracy R, Hennekens C. Inflammation, aspirin and the risk of cardiovascular disease in apparently healthy men. New England Journal of Medicine 1997;336:973–979.

    Article  CAS  PubMed  Google Scholar 

  202. Landmesser U, Merten R, Spiekermann S, Buttner K, Drexler H, Hornig B. Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: Relation to endothelium-dependent vasodilation. Circulation 2000;101:2264–2270.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology, Foothills Hospital, 1432, 29th Street, NW, Calgary, AB, T2N 2T9, Canada

    Todd J. Anderson MD, FRCPC

  2. Department of Medicine, University of Calgary, Calgary, AB, Canada

    Todd J. Anderson MD, FRCPC

Authors
  1. Todd J. Anderson MD, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Cardiology Division Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

    Bodh I. Jugdutt

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Kluwer Academic Publishers

About this chapter

Cite this chapter

Anderson, T.J. (2004). Nitric Oxide, Atherosclerosis and the Clinical Relevance of Endothelial Dysfunction. In: Jugdutt, B.I. (eds) The Role of Nitric Oxide in Heart Failure. Springer, Boston, MA. https://doi.org/10.1007/1-4020-7960-5_5

Download citation

  • DOI: https://doi.org/10.1007/1-4020-7960-5_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4020-7736-4

  • Online ISBN: 978-1-4020-7960-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation