Asymmetric dimethylarginine and NO metabolites in patients with acute and chronic coronary heart disease
Abstract
Aim.То study the levels of asymmetric dimethylarginine (ADMA) and NO metabolites in patients with ST elevation acute coronary syndrome (ACS-ST), as well as in patients with stable effort angina (SEA).
Material and methods. The study involved 35 patients: 20 with ACS-ST (mean age 57,4±9,2 years) and 15 with SEA (mean age 57±7,1 years). All participants underwent standard examination and measurement of ADMA and NO metabolite (nitrites, nitrates) concentration in venous blood at admission and after 2 weeks of treatment, with the final examination at 12 months.
Results. At baseline, ACS-ST patients demonstrated significant increase in ADMA and reduction in NO metabolites. After 2 weeks of treatment, no significant difference in NO metabolite levels was observed between two groups. Non-significant difference in pre- and post-treatment ADMA concentration was registered in ACS-ST patients, but this difference reached statistical significance in the subgroup of ACS-ST participants without arterial hypertension. The patients who suffered a recurrent fatal myocardial infarction within the next 12 months, demonstrated higher ADMA concentrations than all ACS individuals.
Conclusion. ACS-ST patients had increased ADMA levels and reduced NO metabolite concentrations. In treated ACS-ST patients, NO metabolite levels increased.
About the Authors
A. S. Galyavich
Kazan State Medical University
Russian Federation
Russian Federation
E. R. Gaynutdinov
Kazan State Medical University
Russian Federation
Russian Federation
References
1. Титов В.Н. Кардинальные Вопросы патогенеза атеросклероза: настоящее и перспективы. Тер архив 2001; 12: 78—82.
2. Teerlink Т. ADMA metabolism and clearance. Vase Med 2005; 10(Suppl 1): S73-81.
3. 3 Lu CW, Xiong Y, He P. Dimethylarginine dimethylaminohydr olase-2 overexpression improves impaired nitric oxide synthesis of endothelial cells induced by glycated protein. Nitric Oxide 2006; 8: 5.
4. MacAllister RJ, Parry H, Kimoto M, et al. Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase. Br J Pharmacol 1996; 119: 1533-40.
5. Bode-Boger SM, Scalera F, Martens-Lobenlioffer J. Asynmietric dimethylarginine (ADMA) accelerates cell senescence. Vase Med 2005; 10(Suppl 1): S65-71.
6. Kielstein JT, Tsikas D, Fliser D. Effects of asymmetric dimethylarginine (ADMA) infusion in humans. Eur J Clin Pharmacol 2006; 62(Suppl 13): 39-44.
7. Chan JR, Boger RH, Bode-Boger SM, et al. Asymmetric dimethylarginine increases mononuclear cell adhesiveness in hypercholesterolemic humans. Arterioscler Thromb Vase Biol 2000; 20:1040-6.
8. Boger RH, Bode-Boger SM, Tsao PS, et al. An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes. JACC 2000; 36: 2287-95.
9. Smirnova IV, Kajstura M, Sawamura T, et al. Asymmetric dimethylarginine upregulates TOX-1 in activated macrophages: role in foam cell formation. Am J Physiol Heart Circ Physiol 2004; 287: H782-9.
10. Boger RH, Bode-Boger SM, Szuba A, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 1998; 98: 1842-7.
11. Tin 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: 987-92.
12. Paiva H, Lehtimaki T, Laakso J, et al. Plasma concentrations of asymmetric dimethylarginine in type 2 diabetes associate with glycemic control and glomerular filtration rate but not with risk factors of vasculopathy. Metabolism 2003; 52: 303—7.
13. Eid HM, Amesen H, Hjerkiim EM, et al. Relationship between obesity, smoking, and the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine. Metabolism 2004; 53: 1574-9.
14. Stuhlinger MC, Oka RK, Graf ЕЁ, et al. Endothelial dysfunction induced by hyperhomocyst (e) inemia: role of asymmetric dimethylarginine. Circulation 2003; 108: 933-8
15. Stuhlinger MC, Tsao PS, Her .III, et al. Homocysteine impairs the nitric oxide synthase pathway: role of asynmietric dimethylarginine. Circulation 2001; 104: 2569-75.
16. Zoccali C, Benedetto FA, Maas R, et al. CREED Investigators. Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease. J Am Soc Nephrol 2002; 13: 490-6.
17. Schulze F, Wesemaim R, Schwedhelm Ц, et al. Determination of asymmetric dimethylarginine (ADMA) using a novel ETISA assay Clin Cliem Tab Med 2004; 42(12): 1377-83.
18. Krempl TK, Maas R, Sydow K, et al. Elevation of asymmetric dimethylarginine in patients with unstable angina and recurrent cardiovascular events. Eur Heart J 2005; 26(18): 1846-51.
19. Bae SW, Sthlinger MC, Yoo HS, et al. Plasma asymmetric dimethylarginine concentrations in newly diagnosed patients with acute myocardial infarction or unstable angina pectoris during two weeks of medical treatment. Am J Cardiol 2005; 95(6): 729-33.
20. Yazici M, Demircan S, Duma K. Association between nitric oxide levels on myocardial injury in non-ST elevation acute coronary syndromes. J Thromb Thrombolysis 2007; 24(2): 145-51."
21. Ruef J, Merz W, Winkelmaim BR. Markers for endothelial dysfunction, but not markers for oxidative stress correlate with classical risk factors and the severity of coronary artery disease. (A subgroup analysis from the Tudwigshafen Risk and Cardiovascular Health Study). Scand Cardiovasc J 2006; 40(5): 274-9.
22. Schnabel R, Blankenberg S, Tubos Б, 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(5): e53-9.
23. Lu TM, Ding YA, Lin SJ, et al. Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention. Eur Heart J 2003; 24(21): 1912-9.
24. Mittermayer E ADMA predicts major adverse cardiovascular events in patients with advanced PAD. Arterioscler Thromb Vase Biology 2006.
25. Zeller M, Korandji C, Guilland JC, et al. Impact of asymmetric dimethylarginine on mortality after acute myocardial infarction. Arterioscler Thromb Vase Biol 2008; 28(5): 954-60.
26. 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(3): 493.el-8.
Review
For citations:
Galyavich A.S., Gaynutdinov E.R. Asymmetric dimethylarginine and NO metabolites in patients with acute and chronic coronary heart disease. Cardiovascular Therapy and Prevention. 2009;8(1):31-34. (In Russ.)
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