Increased Circulating Asymmetric Dimethylarginine (ADMA) Levels in the Active Stage of Behçet’s Syndrome

Zusammenfassung

Es gibt in der Literatur wenige Angaben über die Spiegel von zirkulierendem asymmetrischem Dimethylarginin (ADMA) bei Morbus Behçet (BS). Das Ziel der vorliegenden Studie war 1. die Bestimmung von ADMA-Werten bei männlichen Patienten mit BS, 2. der Vergleich von ADMA-Werten mit gesunden Freiwilligen und 3. die Feststellung, ob es Unterschiede gibt zwischen Patienten mit und ohne Thrombose sowie während des aktiven und inaktiven Stadiums. Bei Patienten mit BS lagen die CRP-Werte höher als bei den Vergleichspersonen. Die durchschnittlichen Werte von ADMA und C-reaktivem Protein (CRP) waren signifikant höher bei Patienten im aktiven Stadium und Patienten mit Thrombose als bei Patienten im inaktiven Stadium und ohne Thrombose. Zusammenfassend konnten wir in Bezug auf die ADMA-Spiegel keine signifikanten Unterschiede finden zwischen Patienten mit BS und gesunden Kontrollpersonen. Die Serum-ADMA-Werte waren aber höher bei Patienten im aktiven Stadium und Patienten mit Thrombose als die von Patienten im inaktiven Stadium und jenen ohne Thrombose.

Abstract

There is little evidence in the literature about circulating asymmetric dimethylarginine (ADMA) levels in Behçet’s syndrome (BS). The aim of the present study was 1. to measure the levels of ADMA in male patients with BS, 2. to compare ADMA levels with healthy volunteers, and 3. to evaluate whether there is any difference between patients both with/without thrombosis and in active/inactive stage. In patients with BS, CRP levels were higher than controls. The mean ADMA and C-reactive protein (CRP) levels were significantly higher in active stage patients and patients with thrombosis than in patients during the inactive stage and without thrombosis. In conclusion, we did not find any significant difference in ADMA levels between patients with BS and healthy controls. Serum ADMA concentrations, however, were higher in active patients and patients with thrombosis than in patients during the inactive stage and patients without thrombosis.

Morbus Behçet - asymmetrisches Dimethylarginin - endotheliale Dysfunktion - Thrombose - aktives Stadium

Behçet’s syndrome - asymmetric dimethylarginine - endothelial dysfunction - thrombosis - active stage

References

• 1 Achan V, Broadhead M, Malaki M. et al . Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase.  Arterioscler Thromb Vasc Biol. 2003;  23 1455-1459
• 2 Andrew P J, Mayer B. Enzymatic function of nitric oxide synthases.  Cardiovasc Res. 1999;  43 521-531
• 3 Atzeni F, Sarzi-Puttini P, Doria A. et al . Behcet’s disease and cardiovascular involvement.  Lupus. 2005;  14 723-726
• 4 Behcet H. Ueber rezidiverende aphtoese, durch ein virus verur sachte Geschwuere am mund am Auge und an den Genitalien.  Dermatol Wochenschr. 1937;  105 1152
• 5 Böger R H, Bode-Böger S M, Thiele W. et al . Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease.  Circulation. 1997;  95 2068-2074
• 6 Buldanlioglu S, Turkmen S, Ayabakan H B. et al . Nitric oxide, lipid peroxidation and antioxidant defence system in patients with active or inactive Behcet’s disease.  Br J Dermatol. 2005;  153 526-530
• 7 Caglar K, Yilmaz M I, Sonmez A. et al . ADMA, proteinuria, and insulin resistance in non-diabetic stage I chronic kidney disease.  Kidney Int. 2006;  70 781-787
• 8 Caliskan M, Yilmaz S, Yildirim E. et al . Endothelial functions are more severely impaired during active disease period in patients with Behcet’s disease.  Clin Rheumatol. 2007;  26 1074-1078
• 9 Chambers J C, Haskard D O, Kooner J S. Vascular endothelial function and oxidative stress mechanisms in patients with Behcet’s syndrome.  J Am Coll Cardiol. 2001;  37 517-520
• 10 Cooke J P. Does ADMA cause endothelial dysfunction?.  Arterioscler Thromb Vasc Biol. 2000;  20 2032-2037
• 11 Cooke J P. Asymmetrical dimethylarginine: the Uber marker?.  Circulation. 2004;  109 1813-1818
• 12 Er H, Evereklioglu C, Cumurcu T. et al . Serum homocysteine level is increased and correlated with endothelin-1 and nitric oxide in Behcet’s disease.  Br J Ophthalmol. 2002;  86 653-657
• 13 Farrell A J, Blake D R. Nitric oxide.  Ann Rheum Dis. 1996;  55 7-20
• 14 Hingorani A D, Cross J, Kharbanda R K. et al . Acute systemic inflammation impairs endothelium-dependent dilatation in humans.  Circulation. 2000;  102 994-999
• 15 International Study Group for Behçet’s Disease . Criteria for diagnosis of Behçet’s disease.  Lancet. 1990;  335 1078-1080
• 16 Karasneh J A, Hajeer A H, Silman A. et al . Polymorphisms in the endothelial nitric oxide synthase gene are associated with Behcet’s disease.  Rheumatology (Oxford). 2005;  44 614-617
• 17 Kiraz S, Ertenli I, Calguneri M. et al . Interactions of nitric oxide and superoxide dismutase in Behcet’s disease.  Clin Exp Rheumatol. 2001;  19 S25-S29
• 18 Krause I, Mader R, Sulkes J. Behçet’s disease in Israel: the influence of ethnic origin on disease expression and severity.  J Rheumatol. 2001;  28 1033-1036
• 19 Lie J T. Vascular involvement in Behçet’s disease: arterial and venous vessels of all sizes.  J Rheumatol. 1992;  19 341-343
• 20 Miyazaki H, Matsuoka H, Cooke J P. Endogenous nitric oxide synthase inhibitor. A novel marker of atherosclerosis.  Circulation. 1999;  99 1141-1146
• 21 Moncada S, Higgs A. The 1-arginine-nitric oxide pathway.  N Engl J Med. 1993;  329 200-212
• 22 Nalbant S, Aktay D, Cingozbay Y. et al . Homocysteine and Behçet disease.  J Clin Rheumatol. 2003;  9 65-66
• 23 Orem A, Vanizor B, Cimsit G. et al . Decreased nitric oxide production in patients with Behcet’s disease.  Dermatology. 1999;  198 33-36
• 24 Ozdemir R, Barutcu I, Sezgin A T. et al . Vascular endothelial function and plasma homocysteine levels in Behcet’s disease.  Am J Cardiol. 2004;  94 522-525
• 25 Ozgurtas T, Oktenli C, Dede M. et al . Metformin and oral contraceptive treatments reduced circulating asymmetric dimethylarginine (ADMA) levels in patients with polycystic ovary syndrome (PCOS).  Atherosclerosis. 2008;  Epub ahead of print
• 26 Sahin M, Arslan C, Naziroglu M. et al . Asymmetric dimethylarginine and nitric oxide levels as signs of endothelial dysfunction in Behcet’s disease.  Ann Clin Lab Sci. 2006;  36 449-454
• 27 Seyahi E, Ugurlu S, Cumali R. et al . Atherosclerosis in Behçet’s syndrome.  Arthritis Rheum. 2005;  52 642
• 28 Vallance P, Leone A, Calver A. et al . Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure.  Lancet. 1992;  339 572-575
• 29 Yesilova Z, Pay S, Oktenli C. et al . Hyperhomocysteinemia in patients with Behçet’s disease: is it due to inflammation or therapy?.  Rheumatol Int. 2005;  25 423-428