Serum Asymmetric Dimethylarginine Levels in Patients with Acute Rheumatic Fever

 

 Buy Article Permissions and Reprints

Abstract

Asymmetric dimethylarginine (ADMA) is an analogue of l-arginine, a naturally occurring product of metabolism found in human circulation. It is an endogenous inhibitor of nitric oxide production. Acute rheumatic fever (ARF) is a delayed immunologically mediated autoimmune sequel of throat infection by group A β-hemolytic streptococci. As serum ADMA levels have not previously been assessed in patients with ARF, we aimed to investigate ADMA levels in patients with ARF during the acute stage and after anti-inflammatory treatment and compared results with healthy control subjects. The study population consisted of 34 children with ARF (30 patients with carditis and 4 patients without carditis) and 31 healthy control subjects. Erythrocyte sedimentation rate and C-reactive protein values were significantly higher and serum ADMA values were lower, but not statistically significant in patients with ARF during the acute stage when compared with controls. Serum C-reactive protein and erythrocyte sedimentation rate values were significantly decreased in patients with ARF after the treatment when compared with baseline and ADMA levels were increased after the treatment compared with baseline, but this change was not statistically significant. Our study has demonstrated that resolution of acute inflammation in patients with ARF may lead to a mild increase in serum concentration of ADMA. Comprehensive prospective and observational studies are required to confirm our findings and to assess potential interactions between ARF and ADMA levels.

Note

The study was approved by the Ethics Committee of Selcuk University Hospital, and parents were provided written informed consent.

• References

• 1 Siervo M, Corander M, Stranges S, Bluck L. Post-challenge hyperglycaemia, nitric oxide production and endothelial dysfunction: the putative role of asymmetric dimethylarginine (ADMA). Nutr Metab Cardiovasc Dis 2011; 21 (1) 1-10
  CrossrefPubMedGoogle Scholar
• 2 Böger RH, Maas R, Schulze F, Schwedhelm E. Asymmetric dimethylarginine (ADMA) as a prospective marker of cardiovascular disease and mortality—an update on patient populations with a wide range of cardiovascular risk. Pharmacol Res 2009; 60 (6) 481-487
  CrossrefPubMedGoogle Scholar
• 3 Narula J, Chandrasekhar Y, Rahimtoola S. Diagnosis of active rheumatic carditis. The echoes of change. Circulation 1999; 100 (14) 1576-1581
  CrossrefPubMedGoogle Scholar
• 4 Carapetis JR, McDonald M, Wilson NJ. Acute rheumatic fever. Lancet 2005; 366 (9480) 155-168
  CrossrefPubMedGoogle Scholar
• 5 Kemeny E, Grieve T, Marcus R, Sareli P, Zabriskie JB. Identification of mononuclear cells and T cell subsets in rheumatic valvulitis. Clin Immunol Immunopathol 1989; 52 (2) 225-237
  CrossrefPubMedGoogle Scholar
• 6 Settin A, Abdel-Hady H, El-Baz R, Saber I. Gene polymorphisms of TNF-alpha(-308), IL-10(-1082), IL-6(-174), and IL-1Ra(VNTR) related to susceptibility and severity of rheumatic heart disease. Pediatr Cardiol 2007; 28 (5) 363-371
  CrossrefPubMedGoogle Scholar
• 7 Spies CM, Cutolo M, Straub RH, Burmester GR, Buttgereit F. Prednisone chronotherapy. Clin Exp Rheumatol 2011; 29 (5, Suppl 68) S42-S45
  PubMedGoogle Scholar
• 8 Turiel M, Atzeni F, Tomasoni L , et al. Non-invasive assessment of coronary flow reserve and ADMA levels: a case-control study of early rheumatoid arthritis patients. Rheumatology (Oxford) 2009; 48 (7) 834-839
  CrossrefPubMedGoogle Scholar
• 9 Bultink IE, Teerlink T, Heijst JA, Dijkmans BA, Voskuyl AE. Raised plasma levels of asymmetric dimethylarginine are associated with cardiovascular events, disease activity, and organ damage in patients with systemic lupus erythematosus. Ann Rheum Dis 2005; 64 (9) 1362-1365
  CrossrefPubMedGoogle Scholar
• 10 Sari I, Kebapcilar L, Alacacioglu A , et al. Increased levels of asymmetric dimethylarginine (ADMA) in patients with ankylosing spondylitis. Intern Med 2009; 48 (16) 1363-1368
  CrossrefPubMedGoogle Scholar
• 11 Dooley A, Gao B, Bradley N , et al. Abnormal nitric oxide metabolism in systemic sclerosis: increased levels of nitrated proteins and asymmetric dimethylarginine. Rheumatology (Oxford) 2006; 45 (6) 676-684
  CrossrefPubMedGoogle Scholar
• 12 Gu LQ, Zhao L, Zhu W , et al. Relationships between serum levels of thyroid hormones and serum concentrations of asymmetric dimethylarginine (ADMA) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) in patients with Graves' disease. Endocrine 2011; 39 (3) 266-271
  CrossrefPubMedGoogle Scholar
• 13 Committee on Rheumatic Fever, Bacterial Endocarditis of the American Heart Association. Jone's criteria (revised) for guidance in the diagnosis of rheumatic fever. Circulation 1984; 69: 203-208
  CrossrefPubMedGoogle Scholar
• 14 Tani LY. Rheumatic fever and rheumatic heart disease. In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF, , eds. Moss and Adams' Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adult. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008: 1257-1275
  Google Scholar
• 15 Chen BM, Xia LW, Zhao RQ. Determination of N(G),N(G)-dimethylarginine in human plasma by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 1997; 692 (2) 467-471
  CrossrefPubMedGoogle Scholar
• 16 WHO Expert Consultation on Rheumatic Fever and Rheumatic Heart Disease. Rheumatic fever and rheumatic heart disease. World Health Organ Tech Rep Ser 2004; 923: 1-122
  PubMedGoogle Scholar
• 17 Kimball TR, Michelfelder EC. Echocardiography. In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF, , eds. Moss and Adams' Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adult. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008: 95-163
  Google Scholar
• 18 Hafez M, El-Morsy Z, El-Shennawy F , et al. Susceptibility to over production of cytokines in acute rheumatic carditis and their role in the pathogenesis. J Med Sci 2002; 2: 65-73
  CrossrefPubMedGoogle Scholar
• 19 Housby JN, Cahill CM, Chu B , et al. Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes. Cytokine 1999; 11 (5) 347-358
  CrossrefPubMedGoogle Scholar
• 20 Ueda S, Kato S, Matsuoka H , et al. Regulation of cytokine-induced nitric oxide synthesis by asymmetric dimethylarginine: role of dimethylarginine dimethylaminohydrolase. Circ Res 2003; 92 (2) 226-233
  CrossrefPubMedGoogle Scholar
• 21 Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP. Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 1999; 99 (24) 3092-3095
  CrossrefPubMedGoogle Scholar
• 22 Narin F, Narin N, Pasaoğlu H, Halici C, Aslan D. Nitric oxide metabolities in acute rheumatic fever. Tohoku J Exp Med 2003; 199 (3) 135-139
  CrossrefPubMedGoogle Scholar
• 23 Sandoo A, Veldhuijzen van Zanten JJ, Metsios GS, Carroll D, Kitas GD. Vascular function and morphology in rheumatoid arthritis: a systematic review. Rheumatology (Oxford) 2011; 50 (11) 2125-2139
  CrossrefPubMedGoogle Scholar
• 24 Spasovski D, Latifi A, Osmani B , et al. Determination of the diagnostic values of asymmetric dimethylarginine as an indicator for evaluation of the endothelial dysfunction in patients with rheumatoid arthritis. Arthritis (Egypt) 2013; 2013: 818-037
  PubMedGoogle Scholar
• 25 Uner A, Sal E, Doğan M , et al. Investigation of oxidant and antioxidant pathway changes in acute rheumatic fever. Acta Cardiol 2010; 65 (1) 53-57
  CrossrefPubMedGoogle Scholar
• 26 Kurban S, Mehmetoglu I, Oran B, Kiyici A. Homocysteine levels and total antioxidant capacity in children with acute rheumatic fever. Clin Biochem 2008; 41 (1-2) 26-29
  CrossrefPubMedGoogle Scholar
• 27 Oran B, Atabek E, Karaaslan S, Reisli Y, Gültekin F, Erkul Y. Oxygen free radicals in children with acute rheumatic fever. Cardiol Young 2001; 11 (3) 285-288
  CrossrefPubMedGoogle Scholar
• 28 Schroecksnadel K, Weiss G, Stanger O, Teerlink T, Fuchs D. Increased asymmetric dimethylarginine concentrations in stimulated peripheral blood mononuclear cells. Scand J Immunol 2007; 65 (6) 525-529
  CrossrefPubMedGoogle Scholar
• 29 Sydow K, Münzel T. ADMA and oxidative stress. Atheroscler Suppl 2003; 4 (4) 41-51
  PubMedGoogle Scholar
• 30 Pitocco D, Zaccardi F, Di Stasio E , et al. Role of asymmetric-dimethyl-L-arginine (ADMA) and nitrite/nitrate (NOx) in the pathogenesis of oxidative stress in female subjects with uncomplicated type 1 diabetes mellitus. Diabetes Res Clin Pract 2009; 86 (3) 173-176
  CrossrefPubMedGoogle Scholar
• 31 Lücke T, Kanzelmeyer N, Kemper MJ, Tsikas D, Das AM. Developmental changes in the L-arginine/nitric oxide pathway from infancy to adulthood: plasma asymmetric dimethylarginine levels decrease with age. Clin Chem Lab Med 2007; 45 (11) 1525-1530
  PubMedGoogle Scholar
• 32 Zoccali C, Maas R, Cutrupi S , et al. Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections. Nephrol Dial Transplant 2007; 22 (3) 801-806
  CrossrefPubMedGoogle Scholar
• 33 Bode-Böger SM, Scalera F, Kielstein JT , et al. Symmetrical dimethylarginine: a new combined parameter for renal function and extent of coronary artery disease. J Am Soc Nephrol 2006; 17 (4) 1128-1134
  CrossrefPubMedGoogle Scholar
• 34 Baylis C. Arginine, arginine analogs and nitric oxide production in chronic kidney disease. Nat Clin Pract Nephrol 2006; 2 (4) 209-220
  CrossrefPubMedGoogle Scholar