ENDOKRİN HASTALIKLARDA ASİMETRİK DİMETİLARJİNİN (ADMA)

Yıl 2009, Cilt: 22 Sayı: 1, 80 - 84, 11.05.2015

Alev Eroğlu Altınova , Metin Arslan

Öz

Asimetrik dimetilarjinin (ADMA) insanda nitrik oksit biyosentezinin majör inhibitörüdür. Yapılan son çalışmalarda plazma ADMA düzeylerindeki artışın endotel disfonksiyonu ve artmış aterogenez ile ilişkili olduğu gösterilmiştir. Birçok endokrin hastalıkta kardiyovasküler riske katkıda bulunan artmış ADMA düzeyleri saptanmıştır. Bu derleme yazısında ADMA’nın diabetes mellitus, obezite ve tiroid disfonksiyonu gibi çeşitli endokrin hastalıklardaki rolü tartışılacaktır.

Anahtar Kelimeler: ADMA, NO, endokrin hastalıklar, kardiyovasküler risk

Anahtar Kelimeler

ADMA, NO, Endokrin hastalıklar, Kardiyovasküler risk

Kaynakça

• 1. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327: 524-526.
• 2. Böger RH. The emerging role of ADMA as a novel cardiovascular risk factor. Cardiovasc Res 2003; 59: 824-833.
• 3. Chan NN, Chan JC. Asymmetric dimethylarginine (ADMA): a potential link between endothelial dysfunction and cardiovascular diseases in insulin resistance syndrome?. Diabetologia 2002; 45: 1609- 1616.
• 4. Vallance P, Chan N. Endothelial function and nitric oxide: clinical relevance. Heart 2001; 85: 342-350.
• 5. Vallance P, Leone A, Calver A, Collier J, Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992; 339: 572-575.
• 6. Pettersson A, Uggla L, Backman V. Determination of dimethylated arginines in human plasma by highperformance liquid chromatography. J Chromatogr B Biomed Sci Appl 1997; 692: 257-262.
• 7. Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP. Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 1999; 99: 3092- 3095.
• 8. Miyazaki H, Matsuoka H, Cooke JP, et al. Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 1999; 99: 1141- 1146.
• 9. Calver A, Collier J, Leone A, Moncada S, Vallance P. Effect of local intra-arterial asymmetric dimethylarginine (ADMA) on the forearm arteriolar bed of healthy volunteers. J Hum Hypertens 1993; 7: 193-194.
• 10. Furuki K, Adachi H, Matsuoka H, et al. Plasma levels of asymmetric dimethylarginine (ADMA) are related to intima-media thickness of the carotid artery: an epidemiological study. Atherosclerosis 2007; 191: 206-210.
• 11. Schnabel R, Blankenberg S, Lubos E, et al. Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study. Circ Res 2005; 97: e53-e59.
• 12. Schulze F, Lenzen H, Hanefeld C, et al. Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: results from the multicenter Coronary Artery Risk Determination investigating the Influence of ADMA Concentration (CARDIAC) study. Am Heart J 2006; 152: 493.e1-e8.
• 13. Perticone F, Sciacqua A, Maio R, et al. Asymmetric dimethylarginine, L-arginine, and endothelial dysfunction in essential hypertension. J Am Coll Cardiol 2005; 46: 518-523.
• 14. Curgunlu A, Uzun H, Bavunoğlu I, Karter Y, Genç H, Vehid S. Increased circulating concentrations of asymmetric dimethylarginine (ADMA) in white coat hypertension. J Hum Hypertens 2005; 19: 629-633.
• 15. 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.
• 16. Takiuchi S, Fujii H, Kamide K, et al. Plasma asymmetric dimethylarginine and coronary and peripheral endothelial dysfunction in hypertensive patients. Am J Hypertens 2004; 17: 802-808.
• 17. Böger RH, Bode-Böger SM, Szuba A, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 1998; 98: 1842- 1847.
• 18. Böger RH, Lentz SR, Bode-Böger SM, Knapp HR, Haynes WG. Elevation of asymmetrical dimethylarginine may mediate endothelial dysfunction during experimental hyperhomocyst(e)inaemia in humans. Clin Sci (Lond) 2001; 100: 161-167.
• 19. Böger RH, Sydow K, Borlak J, et al. LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ Res 2000; 87: 99-105.
• 20. Jia SJ, Jiang DJ, Hu CP, Zhang XH, Deng HW, Li YJ. Lysophosphatidylcholine-induced elevation of asymmetric dimethylarginine level by the NADPH oxidase pathway in endothelial cells. Vascul Pharmacol 2006; 44: 143-148.
• 21. Eid HM, Arnesen H, Hjerkinn EM, Lyberg T, Seljeflot I. Relationship between obesity, smoking, and the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine. Metabolism 2004; 53: 1574-1579.
• 22. McLaughlin T, Stühlinger M, Lamendola C, et al. Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin-resistant women and fall with weight loss. J Clin Endocrinol Metab 2006; 91: 1896-1900
• 23. Konukoglu D, Uzun H, Firtina S, Cigdem Arica P, Kocael A, Taskin M. Plasma adhesion and inflammation markers: asymmetrical dimethyl-Larginine and secretory phospholipase A2 concentrations before and after laparoscopic gastric banding in morbidly obese patients. Obes Surg 2007; 17: 672-678.
• 24. Krzyzanowska K, Mittermayer F, Krugluger W, et al. Asymmetric dimethylarginine is associated with macrovascular disease and total homocysteine in patients with type 2 diabetes. Atherosclerosis 2006; 189: 236-240.
• 25. Paiva H, Lehtimaki T, Laakso J, et al. Plasma concentrations of asymmetric-dimethyl-arginine in type 2 diabetes associate with glycemic control and glomerular filtration rate but not with risk factors of vasculopathy. Metabolism 2003; 52: 303-307.
• 26. Krzyzanowska K, Mittermayer F, Wolzt M, Schernthaner G. Asymmetric dimethylarginine predicts cardiovascular events in patients with type 2 diabetes. Diabetes Care 2007; 30: 1834-1839.
• 27. Malecki MT, Undas A, Cyganek K, et al. Plasma asymmetric dimethylarginine (ADMA) is associated with retinopathy in Type 2 diabetes mellitus. Diabetes Care 2007; 30: 2899-2901.
• 28. Altinova AE, Arslan M, Sepici-Dincel A, Akturk M, Altan N, Toruner FB. Uncomplicated type 1 diabetes is associated with increased asymmetric dimethylarginine concentrations. J Clin Endocrinol Metab 2007; 92: 1881-1885.
• 29. Tarnow L, Hovind P, Teerlink T, Stehouwer CD, Parving HH. Elevated plasma asymmetric dimethylarginine as a marker of cardiovascular morbidity in early diabetic nephropathy in type 1 diabetes. Diabetes Care 2004; 27: 765-769.
• 30. Lin KY, Ito A, Asagami T, et al. Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 2002; 106: 987- 992.
• 31. Maas R. Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA). Vasc Med 2005; 10(Supp.1): S49-S57.
• 32. Garcia RG, Perez M, Maas R, Schwedhelm E, Böger RH, López-Jaramillo P. Plasma concentrations of asymmetric dimethylarginine (ADMA) in metabolic syndrome. Int J Cardiol 2007; 122: 176-178.
• 33. Demirel F, Bideci A, Cinaz P, et al. Serum leptin, oxidized low density lipoprotein and plasma asymmetric dimethylarginine levels and their relationship with dyslipidaemia in adolescent girls with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2007; 67: 129-134.
• 34. Charitidou C, Farmakiotis D, Zournatzi V, et al. The administration of estrogens, combined with antiandrogens, has beneficial effects on the hormonal features and asymmetric dimethyl-arginine levels, in women with the polycystic ovary syndrome. Atherosclerosis 2007; baskıda
• 35. Krzyzanowska K, Mittermayer F, Schnack C, Hofer M, Wolzt M, Schernthaner G. Circulating ADMA concentrations are elevated in hypopituitary adults with and without growth hormone deficiency. Eur J Clin Invest 2005; 35: 208-213.
• 36. Arikan E, Karadag CH, Guldiken S. Asymmetric dimethylarginine levels in thyroid diseases. J Endocrinol Invest 2007; 30: 186-191.
• 37. Hermenegildo C, Medina P, Peiró M, et al. Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in hyperthyroid patients. J Clin Endocrinol Metab 2002; 87: 5636-5640.
• 38. Ozcan O, Cakir E, Yaman H, et al. The effects of thyroxine replacement on the levels of serum asymmetric dimethylarginine (ADMA) and other biochemical cardiovascular risk markers in patients with subclinical hypothyroidism. Clin Endocrinol (Oxf) 2005; 63: 203-206.