Nutrition, Metabolism & Cardiovascular Diseases
Volume 20, Issue 2 , Pages 140-146 , February 2010

Endothelial dysfunction in metabolic syndrome: Prevalence, pathogenesis and management

  • K. Tziomalos

      Affiliations

    • Department of Clinical Biochemistry (Vascular Prevention Clinic), Royal Free Hospital Campus, University College Medical School, University College London (UCL), London, UK
    • Department of Surgery, Royal Free Hospital Campus, University College Medical School, University College London (UCL), London, UK
    • ,
  • V.G. Athyros

      Affiliations

    • Second Propedeutic Department of Internal Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece
    • ,
  • A. Karagiannis

      Affiliations

    • Second Propedeutic Department of Internal Medicine, Aristotle University, Hippokration Hospital, Thessaloniki, Greece
    • ,
  • D.P. Mikhailidis

      Affiliations

    • Department of Clinical Biochemistry (Vascular Prevention Clinic), Royal Free Hospital Campus, University College Medical School, University College London (UCL), London, UK
    • Department of Surgery, Royal Free Hospital Campus, University College Medical School, University College London (UCL), London, UK
    • Corresponding Author InformationCorresponding author at: Department of Clinical Biochemistry, Royal Free Hospital Campus, University College Medical School, University College London (UCL), Pond Street, London NW3 2QG, UK. Tel.: +44 20 7830 2258; fax: +44 20 7830 2235.

Received 9 March 2009 ,Revised 9 June 2009 ,Accepted 3 August 2009.

References 

  1. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735–2752
  2. Ford ES. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S. Diabetes Care. 2005;28:2745–2749
  3. Grundy SM. Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol. 2008;28:629–636
  4. Athyros VG, Ganotakis ES, Elisaf M, Mikhailidis DP. The prevalence of the metabolic syndrome using the National Cholesterol Educational Program and International Diabetes Federation definitions. Curr Med Res Opin. 2005;21:1157–1159
  5. Ford ES, Li C, Sattar N. Metabolic syndrome and incident diabetes: current state of the evidence. Diabetes Care. 2008;31:1898–1904
  6. Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol. 2007;49:403–414
  7. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115–126
  8. Kullo IJ, Malik AR. Arterial ultrasonography and tonometry as adjuncts to cardiovascular risk stratification. J Am Coll Cardiol. 2007;49:1413–1426
  9. Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation. 2006;113:1888–1904
  10. Rossi R, Cioni E, Nuzzo A, Origliani G, Modena MG. Endothelial-dependent vasodilation and incidence of type 2 diabetes in a population of healthy postmenopausal women. Diabetes Care. 2005;28:702–707
  11. Perticone F, Maio R, Sciacqua A, Andreozzi F, Iemma G, Perticone M, et al. Endothelial dysfunction and C-reactive protein are risk factors for diabetes in essential hypertension. Diabetes. 2008;57:167–171
  12. Benjamin EJ, Larson MG, Keyes MJ, Mitchell GF, Vasan RS, Keaney JF, et al. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation. 2004;109:613–619
  13. McVeigh GE, Brennan GM, Johnston GD, McDermott BJ, McGrath LT, Henry WR, et al. Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1992;35:771–776
  14. Brook RD, Bard RL, Rubenfire M, Ridker PM, Rajagopalan S. Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults. Am J Cardiol. 2001;88:1264–1269
  15. Lupattelli G, Lombardini R, Schillaci G, Ciuffetti G, Marchesi S, Siepi D, et al. Flow-mediated vasoactivity and circulating adhesion molecules in hypertriglyceridemia: association with small, dense LDL cholesterol particles. Am Heart J. 2000;140:521–526
  16. Kuvin JT, Patel AR, Sidhu M, Rand WM, Sliney KA, Pandian NG, et al. Relation between high-density lipoprotein cholesterol and peripheral vasomotor function. Am J Cardiol. 2003;92:275–279
  17. Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115:1285–1295
  18. Barac A, Campia U, Panza JA. Methods for evaluating endothelial function in humans. Hypertension. 2007;49:748–760
  19. Festa A, D'Agostino R, Mykkanen L, Tracy RP, Zaccaro DJ, Hales CN, et al. Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a large population with different states of glucose tolerance. The Insulin Resistance Atherosclerosis Study (IRAS). Arterioscler Thromb Vasc Biol. 1999;19:562–568
  20. Potter van Loon BJ, Kluft C, Radder JK, Blankenstein MA, Meinders AE. The cardiovascular risk factor plasminogen activator inhibitor type 1 is related to insulin resistance. Metabolism. 1993;42:945–949
  21. Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia. 1989;32:219–226
  22. Esposito K, Ciotola M, Carleo D, Schisano B, Saccomanno F, Sasso FC, et al. Effect of rosiglitazone on endothelial function and inflammatory markers in patients with the metabolic syndrome. Diabetes Care. 2006;29:1071–1076
  23. Dell'Omo G, Penno G, Pucci L, Mariani M, Del PS, Pedrinelli R. Abnormal capillary permeability and endothelial dysfunction in hypertension with comorbid Metabolic Syndrome. Atherosclerosis. 2004;172:383–389
  24. Hamburg NM, Larson MG, Vita JA, Vasan RS, Keyes MJ, Widlansky ME, et al. Metabolic syndrome, insulin resistance, and brachial artery vasodilator function in Framingham Offspring participants without clinical evidence of cardiovascular disease. Am J Cardiol. 2008;101:82–88
  25. Lteif AA, Han K, Mather KJ. Obesity, insulin resistance, and the metabolic syndrome: determinants of endothelial dysfunction in whites and blacks. Circulation. 2005;112:32–38
  26. Bahia L, Aguiar LG, Villela N, Bottino D, Godoy-Matos AF, Geloneze B, et al. Relationship between adipokines, inflammation, and vascular reactivity in lean controls and obese subjects with metabolic syndrome. Clinics. 2006;61:433–440
  27. Bahia L, Aguiar LG, Villela N, Bottino D, Godoy-Matos AF, Geloneze B, et al. Adiponectin is associated with improvement of endothelial function after rosiglitazone treatment in non-diabetic individuals with metabolic syndrome. Atherosclerosis. 2007;195:138–146
  28. Lind L. Endothelium-dependent vasodilation, insulin resistance and the metabolic syndrome in an elderly cohort: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Atherosclerosis. 2008;196:795–802
  29. Title LM, Lonn E, Charbonneau F, Fung M, Mather KJ, Verma S, et al. Relationship between brachial artery flow-mediated dilatation, hyperemic shear stress, and the metabolic syndrome. Vasc Med. 2008;13:263–270
  30. Blanco-Colio LM, Martin-Ventura JL, de TE, Farsang C, Gaw A, Gensini G, et al. Elevated ICAM-1 and MCP-1 plasma levels in subjects at high cardiovascular risk are diminished by atorvastatin treatment. Atorvastatin on Inflammatory Markers study: a substudy of Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration. Am Heart J. 2007;153:881–888
  31. Anand SS, Yi Q, Gerstein H, Lonn E, Jacobs R, Vuksan V, et al. Relationship of metabolic syndrome and fibrinolytic dysfunction to cardiovascular disease. Circulation. 2003;108:420–425
  32. You T, Nicklas BJ, Ding J, Penninx BW, Goodpaster BH, Bauer DC, et al. The metabolic syndrome is associated with circulating adipokines in older adults across a wide range of adiposity. J Gerontol A Biol Sci Med Sci. 2008;63:414–419
  33. Mertens I, Verrijken A, Michiels JJ, Van der PM, Ruige JB, Van Gaal LF. Among inflammation and coagulation markers, PAI-1 is a true component of the metabolic syndrome. Int J Obes (Lond). 2006;30:1308–1314
  34. Piatti PM, Monti LD, Conti M, Baruffaldi L, Galli L, Phan CV, et al. Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in humans. Diabetes. 1996;45:316–321
  35. Leoncini G, Ratto E, Viazzi F, Vaccaro V, Parodi D, Parodi A, et al. Metabolic syndrome is associated with early signs of organ damage in nondiabetic, hypertensive patients. J Intern Med. 2005;257:454–460
  36. Chen J, Muntner P, Hamm LL, Jones DW, Batuman V, Fonseca V, et al. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med. 2004;140:167–174
  37. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15:539–553
  38. Panza JA, Quyyumi AA, Brush JE, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323:22–27
  39. Williams SB, Cusco JA, Roddy MA, Johnstone MT, Creager MA. Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus. J Am Coll Cardiol. 1996;27:567–574
  40. Rodriguez CJ, Miyake Y, Grahame-Clarke C, Di Tullio MR, Sciacca RR, Boden-Albala B, et al. Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus. Am J Cardiol. 2005;96:1273–1277
  41. Vehkavaara S, Seppala-Lindroos A, Westerbacka J, Groop PH, Yki-Jarvinen H. In vivo endothelial dysfunction characterizes patients with impaired fasting glucose. Diabetes Care. 1999;22:2055–2060
  42. Henry RM, Ferreira I, Kostense PJ, Dekker JM, Nijpels G, Heine RJ, et al. Type 2 diabetes is associated with impaired endothelium-dependent, flow-mediated dilation, but impaired glucose metabolism is not; The Hoorn Study. Atherosclerosis. 2004;174:49–56
  43. Beckman JA, Goldfine AB, Gordon MB, Creager MA. Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans. Circulation. 2001;103:1618–1623
  44. Title LM, Cummings PM, Giddens K, Nassar BA. Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: an effect prevented by vitamins C and E. J Am Coll Cardiol. 2000;36:2185–2191
  45. Houben AJ, Schaper NC, de Haan CH, Huvers FC, Slaaf DW, de Leeuw PW, et al. Local 24-h hyperglycemia does not affect endothelium-dependent or -independent vasoreactivity in humans. Am J Physiol. 1996;270:H2014–H2020
  46. Perticone F, Ceravolo R, Candigliota M, Ventura G, Iacopino S, Sinopoli F, et al. Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: protective effect of vitamin C. Diabetes. 2001;50:159–165
  47. Arcaro G, Zamboni M, Rossi L, Turcato E, Covi G, Armellini F, et al. Body fat distribution predicts the degree of endothelial dysfunction in uncomplicated obesity. Int J Obes Relat Metab Disord. 1999;23:936–942
  48. Lupattelli G, Marchesi S, Roscini AR, Siepi D, Gemelli F, Pirro M, et al. Direct association between high-density lipoprotein cholesterol and endothelial function in hyperlipemia. Am J Cardiol. 2002;90:648–650
  49. Lundman P, Eriksson MJ, Stuhlinger M, Cooke JP, Hamsten A, Tornvall P. Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine. J Am Coll Cardiol. 2001;38:111–116
  50. Schnell GB, Robertson A, Houston D, Malley L, Anderson TJ. Impaired brachial artery endothelial function is not predicted by elevated triglycerides. J Am Coll Cardiol. 1999;33:2038–2043
  51. 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
  52. Ghiadoni L, Penno G, Giannarelli C, Plantinga Y, Bernardini M, Pucci L, et al. Metabolic syndrome and vascular alterations in normotensive subjects at risk of diabetes mellitus. Hypertension. 2008;51:440–445
  53. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37:1595–1607
  54. Sierra-Johnson J, Johnson BD, Allison TG, Bailey KR, Schwartz GL, Turner ST. Correspondence between the adult treatment panel III criteria for metabolic syndrome and insulin resistance. Diabetes Care. 2006;29:668–672
  55. Hivert MF, Sullivan LM, Fox CS, Nathan DM, D'Agostino RB, Wilson PW, et al. Associations of adiponectin, resistin, and tumor necrosis factor-alpha with insulin resistance. J Clin Endocrinol Metab. 2008;93:3165–3172
  56. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest. 1994;94:1172–1179
  57. 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
  58. Laakso M, Edelman SV, Brechtel G, Baron AD. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. J Clin Invest. 1990;85:1844–1852
  59. Arcaro G, Cretti A, Balzano S, Lechi A, Muggeo M, Bonora E, et al. Insulin causes endothelial dysfunction in humans: sites and mechanisms. Circulation. 2002;105:576–582
  60. Cardillo C, Nambi SS, Kilcoyne CM, Choucair WK, Katz A, Quon MJ, et al. Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation. 1999;100:820–825

PII: S0939-4753(09)00189-6

doi: 10.1016/j.numecd.2009.08.006

Nutrition, Metabolism & Cardiovascular Diseases
Volume 20, Issue 2 , Pages 140-146 , February 2010

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