Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

The endothelial cell in health and disease: its function, dysfunction, measurement and therapy

Abstract

Endothelial cells have numerous endocrine functions and contribute to a variety of processes, including penile erection and vasodilation. Endothelial dysfunction is associated with cardiovascular risk factors and has been implicated in the pathogenesis of atherosclerosis and ED. This study reviews endothelial function, in addition to endothelial dysfunction and its role in atherosclerosis and ED. Measurement of endothelial function is reviewed, including catheter-based methods, venous occlusion plethysmography, high-frequency ultrasound, peripheral arterial tonometry, digital pulse amplitude tonometry, digital thermal monitoring, the L-arginine test and measurement of compounds released by endothelial cells. Therapy and medications that improve endothelial function are reviewed. As the scientific community learns more about the importance of the endothelium, it is increasingly important for the clinician to understand endothelial function, dysfunction, measurement of endothelial function and therapies that affect this remarkable cell type.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Ross R . The pathogenesis of atherosclerosis. N Engl J Med 1986; 314: 488–500.

    Article  CAS  PubMed  Google Scholar 

  2. Henderson AH . St Cyres lecture. Endothelium in control. Br Heart J 1991; 65: 116–125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111–1115.

    Article  CAS  PubMed  Google Scholar 

  4. Kaiser DR, Billups K, Mason C, Wetterling R, Lundberg JL, Bank AJ . Impaired brachial artery endothelium-dependent and -independent vasodilation in men with erectile dysfunction and no other clinical cardiovascular disease. J Am Coll Cardiol 2004; 43: 179–184.

    Article  PubMed  Google Scholar 

  5. Meredith IT, Yeung AC, Weidinger FF, Anderson TJ, Uehata A, Ryan Jr TJ et al. Role of impaired endothelium-dependent vasodilation in ischemic manifestations of coronary artery diease. Circulation 1993; 87 (Suppl V): V56–V66.

    Google Scholar 

  6. De AL, Marfella MA, Siniscalchi M, Marino L, Nappo F, Giugliano F et al. Erectile and endothelial dysfunction in Type II diabetes: a possible link. Diabetologia 2001; 44: 1155–1160.

    Article  Google Scholar 

  7. Saenz de Tejada I, Goldstein I, Azadzoi K, Krane RJ, Cohen RA . Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. N Engl J Med 1989; 320: 1025–1030.

    Article  CAS  PubMed  Google Scholar 

  8. Francavilla S, Properzi G, Bellini C, Marino G, Ferri C, Santucci A . Endothelin-1 in diabetic and nondiabetic men with erectile dysfunction. J Urol 1997; 158: 1770–1774.

    Article  CAS  PubMed  Google Scholar 

  9. Bocchio M, Desideri G, Scarpelli P, Necozione S, Properzi G, Spartera C et al. Endothelial cell activation in men with erectile dysfunction without cardiovascular risk factors and overt vascular damage. J Urol 2004; 171: 1601–1604.

    Article  PubMed  Google Scholar 

  10. Jackson G . Prevention of cardiovascular disease by the early identification of erectile dysfunction. Int J Impot Res 2008; 20 (Suppl 2): S9–S14.

    Article  PubMed  Google Scholar 

  11. Giuliano F . New horizons in erectile and endothelial dysfunction research and therapies. Int J Impot Res 2008; 20 (Suppl 2): S2–S8.

    Article  PubMed  Google Scholar 

  12. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB . Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54–61.

    Article  CAS  PubMed  Google Scholar 

  13. Panza JA, Quyyumi AA, Callahan TS, Epstein SE . Effect of antihypertensive treatment on endothelium-dependent vascular relaxation in patients with essential hypertension. J Am Coll Cardiol 1993; 21: 1145–1151.

    Article  CAS  PubMed  Google Scholar 

  14. Chowienczyk PJ, Watts GF, Cockcroft JR, Ritter JM . Impaired endothelium-dependent vasodilation of forearm resistance vessels in hypercholesterolaemia. Lancet 1992; 340: 1430–1432.

    Article  CAS  PubMed  Google Scholar 

  15. Dakak N, Gilligan DM, Andrews NP, Diodati JG, Panza JA, Schenke WH et al. Peripheral vascular endothelial dysunction in patients with multiple coronary risk factors (Abstract). Circulation 1993; 88: I-618.

    Google Scholar 

  16. Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, Robinson J et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 1993; 88 (5 Part 1): 2149–2155.

    Article  CAS  PubMed  Google Scholar 

  17. Hijmering ML, Stroes ES, Pasterkamp G, Sierevogel M, Banga JD, Rabelink TJ . Variability of flow mediated dilation: consequences for clinical application. Atherosclerosis 2001; 157: 369–373.

    Article  CAS  PubMed  Google Scholar 

  18. 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: 1468–1474.

    Article  CAS  PubMed  Google Scholar 

  19. Drexler H, Zeiher AM, Wollschlager H, Meinertz T, Just H, Bonzel T . Flow-dependent coronary artery dilatation in humans. Circulation 1989; 80: 466–474.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 1986; 315: 1046–1051.

    Article  CAS  PubMed  Google Scholar 

  22. Corretti MC, Plotnick GD, Vogel RA . Technical aspects of evaluating brachial artery vasodilatation using high-frequency ultrasound. Am J Physiol 1995; 268 (4 Part 2): H1397–H1404.

    CAS  PubMed  Google Scholar 

  23. McLenachan JM, Vita J, Fish DR, Treasure CB, Cox DA, Ganz P et al. Early evidence of endothelial vasodilator dysfunction at coronary branch points. Circulation 1990; 82: 1169–1173.

    Article  CAS  PubMed  Google Scholar 

  24. Fish RD, Nabel EG, Selwyn AP, Ludmer PL, Mudge GH, Kirshenbaum JM et al. Responses of coronary arteries of cardiac transplant patients to acetylcholine. J Clin Invest 1988; 81: 21–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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: 287–291.

    Article  CAS  PubMed  Google Scholar 

  26. Quyyumi AA . Endothelial function in health and disease: new insights into the genesis of cardiovascular disease. Am J Med 1998; 105 (1A): 32S–39S.

    Article  CAS  PubMed  Google Scholar 

  27. Bivalacqua TJ, Usta MF, Champion HC, Kadowitz PJ, Hellstrom WJ . Endothelial dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease. J Androl 2003; 24 (6 Suppl): S17–S37.

    Article  CAS  PubMed  Google Scholar 

  28. Katz SD, Biasucci L, Sabba C, Strom JA, Jondeau G, Galvao M et al. Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure. J Am Coll Cardiol 1992; 19: 918–925.

    Article  CAS  PubMed  Google Scholar 

  29. Modena MG, Bonetti L, Coppi F, Bursi F, Rossi R . Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women. J Am Coll Cardiol 2002; 40: 505–510.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  31. Lieberman EH, Knab ST, Creager MA . Nitric oxide mediates the vasodilator response to flow in humans (Abstract). Circulation 1994; 90: I-138.

    Google Scholar 

  32. Reis SE, Holubkov R, Conrad Smith AJ, Kelsey SF, Sharaf BL, Reichek N et al. Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. Am Heart J 2001; 141: 735–741.

    Article  CAS  PubMed  Google Scholar 

  33. Kaski JC . Pathophysiology and management of patients with chest pain and normal coronary arteriograms (cardiac syndrome X). Circulation 2004; 109: 568–572.

    Article  PubMed  Google Scholar 

  34. Panting JR, Gatehouse PD, Yang GZ, Grothues F, Firmin DN, Collins P et al. Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med 2002; 346: 1948–1953.

    Article  PubMed  Google Scholar 

  35. Hein TW, Kuo L . cAMP-independent dilation of coronary arterioles to adenosine: role of nitric oxide, G proteins, and K(ATP) channels. Circ Res 1999; 85: 634–642.

    Article  CAS  PubMed  Google Scholar 

  36. Quyyumi AA, Husain S, Mulcahy D, Andrews NP, Mincemoyer R, Panza JA et al. Nitric oxide activity in the human coronary and peripheral circulation (Abstract). Circulation 1992; 92: I-769.

    Google Scholar 

  37. Takase B, Akima T, Uehata A, Katushika S, Isojima K, Arakawa K . Close relation between endothelium-dependent flow-mediated dilation in coronary and brachial artery in human (Abstract). J Am Coll Cardiol 1998; 31: 359A.

    Article  Google Scholar 

  38. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995; 26: 1235–1241.

    Article  CAS  PubMed  Google Scholar 

  39. Neunteufl T, Heher S, Katzenschlager R, Wolfl G, Kostner K, Maurer G . 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 

  40. Targonski PV, Bonetti PO, Pumper GM, Higano ST, Holmes Jr DR, Lerman A . Coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events. Circulation 200310; 107: 2805–2809.

    Article  PubMed  Google Scholar 

  41. Schindler TH, Hornig B, Buser PT, Olschewski M, Magosaki N, Pfisterer M et al. Prognostic value of abnormal vasoreactivity of epicardial coronary arteries to sympathetic stimulation in patients with normal coronary angiograms. Arterioscler Thromb Vasc Biol 2003; 23: 495–501.

    Article  CAS  PubMed  Google Scholar 

  42. Halcox JP, Schenke WH, Zalos G, Mincemoyer R, Prasad A, Waclawiw MA et al. Prognostic value of coronary vascular endothelial dysfunction. Circulation 2002; 106: 653–658.

    Article  PubMed  Google Scholar 

  43. Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes Jr DR, Lerman A . Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000; 101: 948–954.

    Article  CAS  PubMed  Google Scholar 

  44. Schachinger V, Britten MB, Zeiher AM . Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000; 101: 1899–1906.

    Article  CAS  PubMed  Google Scholar 

  45. Schroeder S, Enderle MD, Ossen R, Meisner C, Baumbach A, Pfohl M et al. Noninvasive determination of endothelium-mediated vasodilation as a screening test for coronary artery disease: pilot study to assess the predictive value in comparison with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging. Am Heart J 1999; 138 (4 Part 1): 731–739.

    Article  CAS  PubMed  Google Scholar 

  46. Gokce N, Keaney Jr JF, 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 

  47. Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A et al. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 2001; 104: 191–196.

    Article  CAS  PubMed  Google Scholar 

  48. Heitzer T, Baldus S, von KY, Rudolph V, Meinertz T . Systemic endothelial dysfunction as an early predictor of adverse outcome in heart failure. Arterioscler Thromb Vasc Biol 2005; 25: 1174–1179.

    Article  CAS  PubMed  Google Scholar 

  49. von Mering GO, Arant CB, Wessel TR, McGorray SP, Bairey Merz CN, Sharaf BL et al. Abnormal coronary vasomotion as a prognostic indicator of cardiovascular events in women: results from the National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). Circulation 2004; 109: 722–725.

    Article  PubMed  Google Scholar 

  50. 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.

    Article  CAS  PubMed  Google Scholar 

  51. Gokce N, Keaney Jr JF, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO et al. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol 2003; 41: 1769–1775.

    Article  PubMed  Google Scholar 

  52. Brevetti G, Silvestro A, Schiano V, Chiariello M . Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease: additive value of flow-mediated dilation to ankle–brachial pressure index. Circulation 2003; 108: 2093–2098.

    Article  PubMed  Google Scholar 

  53. Chan SY, Mancini GB, Kuramoto L, Schulzer M, Frohlich J, Ignaszewski A . The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease. J Am Coll Cardiol 2003; 42: 1037–1043.

    Article  CAS  PubMed  Google Scholar 

  54. Fichtlscherer S, Breuer S, Zeiher AM . Prognostic value of systemic endothelial dysfunction in patients with acute coronary syndromes: further evidence for the existence of the ‘vulnerable’ patient. Circulation 2004; 110: 1926–1932.

    Article  PubMed  Google Scholar 

  55. Celermajer DS . Reliable endothelial function testing: at our fingertips? Circulation 2008; 117: 2428–2430.

    Article  PubMed  Google Scholar 

  56. Deanfield JE, Halcox JP, Rabelink TJ . Endothelial function and dysfunction: testing and clinical relevance. Circulation 2007; 115: 1285–1295.

    Article  PubMed  Google Scholar 

  57. Kern MJ, Lerman A, Bech JW, De BB, Eeckhout E, Fearon WF et al. Physiological assessment of coronary artery disease in the cardiac catheterization laboratory: a scientific statement from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology. Circulation 2006; 114: 1321–1341.

    Article  PubMed  Google Scholar 

  58. Sorensen KE, Celermajer DS, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Thomas O et al. Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility. Br Heart J 1995; 74: 247–253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Benjamin N, Calver A, Collier J, Robinson B, Vallance P, Webb D . Measuring forearm blood flow and interpreting the responses to drugs and mediators. Hypertension 1995; 25: 918–923.

    Article  CAS  PubMed  Google Scholar 

  60. Hayward CS, Kraidly M, Webb CM, Collins P . Assessment of endothelial function using peripheral waveform analysis: a clinical application. J Am Coll Cardiol 2002; 40: 521–528.

    Article  CAS  PubMed  Google Scholar 

  61. Cohn JN, Quyyumi AA, Hollenberg NK, Jamerson KA . Surrogate markers for cardiovascular disease: functional markers. Circulation 2004; 109 (25 Suppl 1): IV31–IV46.

    PubMed  Google Scholar 

  62. Wilkinson IB, Hall IR, MacCallum H, Mackenzie IS, McEniery CM, van der Arend BJ et al. Pulse-wave analysis: clinical evaluation of a noninvasive, widely applicable method for assessing endothelial function. Arterioscler Thromb Vasc Biol 2002; 22: 147–152.

    Article  CAS  PubMed  Google Scholar 

  63. Mitchell GF, Vita JA, Larson MG, Parise H, Keyes MJ, Warner E et al. Cross-sectional relations of peripheral microvascular function, cardiovascular disease risk factors, and aortic stiffness: the Framingham Heart Study. Circulation 2005; 112: 3722–3728.

    Article  PubMed  Google Scholar 

  64. Nair N, Oka RK, Waring LD, Umoh EM, Taylor CB, Cooke JP . Vascular compliance versus flow-mediated vasodilation: correlation with cardiovascular risk factors. Vasc Med 2005; 10: 275–283.

    Article  PubMed  Google Scholar 

  65. Kuvin JT, Patel AR, Sliney KA, Pandian NG, Sheffy J, Schnall RP et al. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J 2003; 146: 168–174.

    Article  PubMed  Google Scholar 

  66. Hamburg NM, Keyes MJ, Larson MG, Vasan RS, Schnabel R, Pryde MM et al. Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham Heart Study. Circulation 2008; 117: 2467–2474.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Bonetti PO, Pumper GM, Higano ST, Holmes Jr DR, Kuvin JT, Lerman A . Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol 2004; 44: 2137–2141.

    Article  PubMed  Google Scholar 

  68. Rubinshtein R, Kuvin JT, Soffler M, Lennon RJ, Nelson RE, Pumper GM et al. Assessment of endothelial function by peripheral arterial tonometry predicts cardiovascular events beyond the Framingham Risk Score (Abstract). J Am Coll Cardiol 2009; 53 (Suppl A): A457.

    Google Scholar 

  69. Gul KM, Ahmadi N, Wang Z, Jamieson C, Nasir K, Metcalfe R et al. Digital thermal monitoring of vascular function: a novel tool to improve cardiovascular risk assessment. Vasc Med 2009; 14: 143–148.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Ahmadi N, Hajsadeghi F, Gul K, Vane J, Usman N, Flores F et al. Relations between digital thermal monitoring of vascular function, the Framingham risk score, and coronary artery calcium score. J Cardiovasc Comput Tomogr 2008; 2: 382–388.

    Article  PubMed  Google Scholar 

  71. Ahmadi N, Nabavi V, Nuguri V, Hajsadeghi F, Flores F, Akhtar M et al. Low fingertip temperature rebound measured by digital thermal monitoring strongly correlates with the presence and extent of coronary artery disease diagnosed by 64-slice multi-detector computed tomography. Int J Cardiovasc Imaging 2009; 25: 725–738.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Ahmadi N, Usman N, Shim J, Nuguri V, Vasinrapee P, Hajsadeghi F et al. Vascular dysfunction measured by fingertip thermal monitoring is associated with the extent of myocardial perfusion defect. J Nucl Cardiol 2009; 16: 431–439.

    Article  PubMed  Google Scholar 

  73. Budoff MJ, Ahmadi N, Gul KM, Liu ST, Flores FR, Tiano J et al. Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: a randomized clinical trial. Prev Med 2009; 49: 101–107.

    Article  CAS  PubMed  Google Scholar 

  74. Giugliano D, Marfella R, Verrazzo G, Acampora R, Nappo F, Ziccardi P et al. -arginine for testing endothelium-dependent vascular functions in health and disease. Am J Physiol 1997; 273 (3 Part 1): E606–E612.

    CAS  PubMed  Google Scholar 

  75. Ridker PM, Hennekens CH, 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 

  76. Hwang SJ, Ballantyne CM, Sharrett AR, Smith LC, Davis CE, Gotto Jr AM et al. Circulating adhesion molecules VCAM-1, ICAM-1, and E-selectin in carotid atherosclerosis and incident coronary heart disease cases: the Atherosclerosis Risk In Communities (ARIC) study. Circulation 1997; 96: 4219–4225.

    Article  CAS  PubMed  Google Scholar 

  77. Speel TG, van LH, Wijkstra H, Meuleman EJ . Penile duplex pharmaco-ultrasonography revisited: revalidation of the parameters of the cavernous arterial response. J Urol 2003; 169: 216–220.

    Article  CAS  PubMed  Google Scholar 

  78. Aversa A, Bruzziches R, Spera G . Diagnosing erectile dysfunction: the penile dynamic colour duplex ultrasound revisited. Int J Androl 2005; 28 (Suppl 2): 61–63.

    Article  PubMed  Google Scholar 

  79. Meuleman EJ, Bemelmans BL, Doesburg WH, van Asten WN, Skotnicki SH, Debruyne FM . Penile pharmacological duplex ultrasonography: a dose-effect study comparing papaverine, papaverine/phentolamine and prostaglandin E1. J Urol 1992; 148: 63–66.

    Article  CAS  PubMed  Google Scholar 

  80. Speel TG, Bleumer I, Diemont WL, van der Maas MC, Wijkstra H, Meuleman EJ . The value of sildenafil as mode of stimulation in pharmaco-penile duplex ultrasonography. Int J Impot Res 2001; 13: 189–191.

    Article  CAS  PubMed  Google Scholar 

  81. Copel L, Katz R, Blachar A, Sosna J, Sheiman RG . Clinical and duplex US assessment of effects of sildenafil on cavernosal arteries of the penis: comparison with intracavernosal injection of vasoactive agents—initial experience. Radiology 2005; 237: 986–991.

    Article  PubMed  Google Scholar 

  82. Ucar G, Secil M, Demir O, Demir T, Comlekci A, Uysal S et al. The combined use of brachial artery flow-mediated dilatation and carotid artery intima-media thickness measurements may be a method to determine vasculogenic erectile dysfunction. Int J Impot Res 2007; 19: 577–583.

    Article  CAS  PubMed  Google Scholar 

  83. Mazo E, Gamidov S, Iremashvili V . The effect of vardenafil on endothelial function of brachial and cavernous arteries. Int J Impot Res 2006; 18: 464–469.

    Article  CAS  PubMed  Google Scholar 

  84. Mazo E, Gamidov S, Anranovich S, Iremashvili V . Testing endothelial function of brachial and cavernous arteries in patients with erectile dysfunction. J Sex Med 2006; 3: 323–330.

    Article  PubMed  Google Scholar 

  85. Demir O, Demir T, Kefi A, Secil M, Comlekci A, Yesil S et al. Penile vascular impairment in erectile dysfunction patients with metabolic syndrome: penile Doppler ultrasound findings. Urol Int 2009; 82: 175–178.

    Article  CAS  PubMed  Google Scholar 

  86. Kaya C, Ergelen M, Ilktac A, Karaman MI . Impaired elasticity of aorta in patients with erectile dysfunction. Urology 2007; 70: 558–562.

    Article  PubMed  Google Scholar 

  87. Proietti M, Aversa A, Letizia C, Rossi C, Menghi G, Bruzziches R et al. Erectile dysfunction in systemic sclerosis: effects of longterm inhibition of phosphodiesterase type-5 on erectile function and plasma endothelin-1 levels. J Rheumatol 2007; 34: 1712–1717.

    CAS  PubMed  Google Scholar 

  88. Esposito K, Ciotola M, Giugliano F, Sardelli L, Giugliano F, Maiorino MI et al. Phenotypic assessment of endothelial microparticles in diabetic and nondiabetic men with erectile dysfunction. J Sex Med 2008; 5: 1436–1442.

    Article  PubMed  Google Scholar 

  89. El Melegy NT, Ali ME, Awad EM . Plasma levels of endothelin-1, angiotensin II, nitric oxide and prostaglandin E in the venous and cavernosal blood of patients with erectile dysfunction. BJU Int 2005; 96: 1079–1086.

    Article  CAS  PubMed  Google Scholar 

  90. Merla A, Romani GL, Tangherlini A, Di RS, Proietti M, Rosato E et al. Penile cutaneous temperature in systemic sclerosis: a thermal imaging study. Int J Immunopathol Pharmacol 2007; 20: 139–144.

    Article  CAS  PubMed  Google Scholar 

  91. Eaton CB, Liu YL, Mittleman MA, Miner M, Glasser DB, Rimm EB . A retrospective study of the relationship between biomarkers of atherosclerosis and erectile dysfunction in 988 men. Int J Impot Res 2007; 19: 218–225.

    Article  CAS  PubMed  Google Scholar 

  92. Al-Ameri H, Kloner RA . Erectile dysfunction and heart failure: the role of phosphodiesterase type 5 inhibitors. Int J Impot Res 2009; 21: 149–157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Tamler R, Bar-Chama N . Assessment of endothelial function in the patient with erectile dysfunction: an opportunity for the urologist. Int J Impot Res 2008; 20: 370–377.

    Article  CAS  PubMed  Google Scholar 

  94. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P . Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 154–160.

    Article  CAS  PubMed  Google Scholar 

  95. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD . Postmenopausal hormone replacement therapy: scientific review. JAMA 2002; 288: 872–881.

    Article  CAS  PubMed  Google Scholar 

  96. Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet 2007; 370: 575–579.

    Article  PubMed  Google Scholar 

  97. Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA et al. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 2002; 106: 2881–2883.

    Article  CAS  PubMed  Google Scholar 

  98. Loukogeorgakis SP, Panagiotidou AT, Broadhead MW, Donald A, Deanfield JE, MacAllister RJ . Remote ischemic preconditioning provides early and late protection against endothelial ischemia–reperfusion injury in humans: role of the autonomic nervous system. J Am Coll Cardiol 2005; 46: 450–456.

    Article  CAS  PubMed  Google Scholar 

  99. Raitakari O, Viikari J, Ronnemaa T, Valimaki I, Juonala M, Magnussen C . The cardiovascular risk in Young Finns Study. The Cardiovascular Risk in Young Finns Study 2009; Available at: URL: http://vanha.med.utu.fi/cardio/youngfinnsstudy/ultrasound.html. Accessed September 8, 2009.

  100. Ockene JK, Kuller LH, Svendsen KH, Meilahn E . The relationship of smoking cessation to coronary heart disease and lung cancer in the Multiple Risk Factor Intervention Trial (MRFIT). Am J Public Health 1990; 80: 954–958.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. 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 

  102. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486–2497.

    Article  Google Scholar 

  103. Esposito K, Giugliano F, Di PC, Giugliano G, Marfella R, D’Andrea F et al. Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. JAMA 2004; 291: 2978–2984.

    Article  CAS  PubMed  Google Scholar 

  104. Bai Y, Sun L, Yang T, Sun K, Chen J, Hui R . Increase in fasting vascular endothelial function after short-term oral L-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2009; 89: 77–84.

    Article  CAS  PubMed  Google Scholar 

  105. Tousoulis D, Boger RH, Antoniades C, Siasos G, Stefanadi E, Stefanadis C . Mechanisms of disease: L-arginine in coronary atherosclerosis—a clinical perspective. Nat Clin Pract Cardiovasc Med 2007; 4: 274–283.

    Article  CAS  PubMed  Google Scholar 

  106. Levine GN, Frei B, Koulouris SN, Gerhard MD, Keaney Jr JF, Vita JA . Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 1996; 93: 1107–1113.

    Article  CAS  PubMed  Google Scholar 

  107. Lieberman EH, Gerhard MD, Uehata A, Walsh BW, Selwyn AP, Ganz P et al. Estrogen improves endothelium-dependent, flow-mediated vasodilation in postmenopausal women. Ann Intern Med 1994; 121: 936–941.

    Article  CAS  PubMed  Google Scholar 

  108. Treasure CB, Klein JL, Weintraub WS, Talley JD, Stillabower ME, Kosinski AS et al. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med 1995; 332: 481–487.

    Article  CAS  PubMed  Google Scholar 

  109. Mercuro G, Zoncu S, Saiu F, Sarais C, Rosano GM . Effect of atorvastatin on endothelium-dependent vasodilation in postmenopausal women with average serum cholesterol levels. Am J Cardiol 2002; 90: 747–750.

    Article  CAS  PubMed  Google Scholar 

  110. Grundy SM, Cleeman JI, Merz CN, Brewer Jr HB, Clark LT, Hunninghake DB et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110: 227–239.

    Article  PubMed  Google Scholar 

  111. Shindel AW, Kishore S, Lue TF . Drugs designed to improve endothelial function: effects on erectile dysfunction. Curr Pharm Des 2008; 14: 3758–3767.

    Article  CAS  PubMed  Google Scholar 

  112. Schwartz BG, Kloner RA . How to save a life during a clinic visit for erectile dysfunction by modifying cardiovascular risk factors. Int J Impot Res 2009; 21: 327–335.

    Article  CAS  PubMed  Google Scholar 

  113. Turnbull F . Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003; 362: 1527–1535.

    Article  CAS  PubMed  Google Scholar 

  114. Law MR, Morris JK, Wald NJ . Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ 2009; 338: b1665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Mancini GB, Henry GC, Macaya C, O’Neill BJ, Pucillo AL, Carere RG et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study. Circulation 1996; 94: 258–265.

    Article  CAS  PubMed  Google Scholar 

  116. Ghiadoni L, Virdis A, Magagna A, Taddei S, Salvetti A . Effect of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension. Hypertension 2000; 35 (1 Part 2): 501–506.

    Article  CAS  PubMed  Google Scholar 

  117. Cockcroft JR, Chowienczyk PJ, Brett SE, Chen CP, Dupont AG, Van NL et al. Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO-dependent mechanism. J Pharmacol Exp Ther 1995; 274: 1067–1071.

    CAS  PubMed  Google Scholar 

  118. Baldwin CM, Keam SJ . Nebivolol: in the treatment of hypertension in the US. Am J Cardiovasc Drugs 2009; 9: 253–260.

    Article  CAS  PubMed  Google Scholar 

  119. Brixius K, Middeke M, Lichtenthal A, Jahn E, Schwinger RH . Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men. Clin Exp Pharmacol Physiol 2007; 34: 327–331.

    Article  CAS  PubMed  Google Scholar 

  120. Husain S, Andrews NP, Mulcahy D, Panza JA, Quyyumi AA . Aspirin improves endothelial dysfunction in atherosclerosis. Circulation 1998; 97: 716–720.

    Article  CAS  PubMed  Google Scholar 

  121. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R . Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373: 1849–1860.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R A Kloner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schwartz, B., Economides, C., Mayeda, G. et al. The endothelial cell in health and disease: its function, dysfunction, measurement and therapy. Int J Impot Res 22, 77–90 (2010). https://doi.org/10.1038/ijir.2009.59

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijir.2009.59

Keywords

This article is cited by

Search

Quick links