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Increased asymmetric dimethylarginine in vitamin B12 deficient adolescents

Published online by Cambridge University Press:  20 February 2019

Mehmet Akif Dündar ,
Yasemin Altuner Torun ,
Serkan Fazlı Çelik ,
Emine Kaygı Tartıcı  and
Çiğdem Karakükçü
Mehmet Akif Dündar*
Affiliation:
Department of Pediatrics, Kayseri Training and Research Hospital, Medical Health University, Kayseri, Turkey
Yasemin Altuner Torun
Affiliation:
Division of Pediatric Hematology, Department of Pediatrics, Kayseri Training and Research Hospital, Medical Health University, Kayseri, Turkey
Serkan Fazlı Çelik
Affiliation:
Division of Pediatric Cardiology, Department of Pediatrics, Kayseri Training and Research Hospital, Medical Health University, Kayseri, Turkey
Emine Kaygı Tartıcı
Affiliation:
Department of Pediatrics, Kayseri Training and Research Hospital, Medical Health University, Kayseri, Turkey
Çiğdem Karakükçü
Affiliation:
Department of Biochemistry, Kayseri Training and Research Hospital, Medical Health University, Kayseri, Turkey
*
Author for correspondence: M. A. Dündar, Kayseri Training and Research Hospital, Medical Health University, 38010 Kocasinan, Kayseri, Turkey. Tel: +905053874085; E-mail: [email protected]
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Abstract

Objective

Vitamin B12 deficiency induces hyper-hyperhomocysteinemia by inhibiting intracellular methionine re-methylation. Hyper-hyperhomocysteinemia increases the risk of atherosclerosis. Asymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthase and its level elevates in cardiovascular diseases. In this study, we aimed to examine the relationship between asymmetric dimethylarginine and arterial stiffness and atherosclerosis in adolescents with vitamin B12 deficiency.

Methods

A total of 88 adolescents with age ranging between 11 and 17 years of age were enrolled for this study. Among them, 50 patients had vitamin B12 deficiency <130 pg/ml and 38 healthy controls had B12 >200 pg/ml. In all cases, the levels of asymmetric dimethylarginine were measured with high performance liquid chromatography method. The carotid artery intima media thickness and left ventricular mass index were measured using echocardiography. All these measurements of the study groups were compared.

Results

Both plasma levels of asymmetric dimethylarginine and carotid artery intima media thickness were significantly higher in the vitamin B12 deficiency group than in the control group. Correlation analysis showed significant negative correlation of vitamin B12 with homocysteine, asymmetric dimethylarginine, and carotid artery intima media thickness (p<0.05).

Conclusion

Our results suggest that endothelial dysfunction starts in the early stage of adolescent vitamin B12 deficiency, and vitamin B12-deficient adolescents have increased circulating asymmetric dimethylarginine, showing that endothelial dysfunction and increased carotid artery intima media thickness be related to atherosclerosis.

Keywords

asymmetric dimethylarginineatherosclerosisvitamin B12 deficiency
Type
Original Article
Information
Cardiology in the Young , Volume 29 , Issue 2 , February 2019 , pp. 190 - 194
Copyright
© Cambridge University Press 2019 

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Footnotes

Cite this article: Dündar MA, Torun YA, Çelik SF, Tartıcı EK, Karakükçü Ç. (2019) Increased asymmetric dimethylarginine in vitamin B12 deficient adolescents. Cardiology in the Young page 190 of 194. doi: 10.1017/S104795111800207X

References

1. Lorenz, MW, Markus, HS, Bots, ML, Rosvall, M, Sitzer, M. Prediction of clinical cardiovascular events with carotid intima-media thickness a systematic review and meta-analysis. Circulation 2007; 115: 459–467.Google Scholar
2. Tonelli, M, Sacks, F, Arnold, M, Moye, L, Davis, B, Pfeffer, M, For the Cholesterol and Recurrent Events (CARE) Trial Investigators. Relation between red blood cell distribution width and cardiovascular event rate in people with coronary disease. Circulation 2008; 117: 163–168.Google Scholar
3. Ng, KC, Yong, QW, Chan, SP, Cheng, A. Homocysteine, folate and vitamin B12 as risk factors for acute myocardial infarction in a southeast Asian population. Ann Acad Med Singapore 2002; 31: 636–640.Google Scholar
4. Lorenz, MW, Markus, HS, Bots, ML, Rosvall, M, Sitzer, M. Prediction of clinical cardiovascular events with carotid intima-media thickness a systematic review and meta-analysis. Circulation 2007; 115: 459–467.Google Scholar
5. Virdis, A, Ghiadoni, L, Salvetti, G, Versari, D, Taddei, S, Salvett, A. Hyperhomocysteinemia: Is a novel risk factor in hypertension? J Nephrol 2002; 15: 414–421.Google Scholar
6. Demir, N, Koc, A, Üstyol, L, Peker, E, Abuhandan, M. Clinical and neurological findings of severe vitamin B12 deficiency in infancy and importance of early diagnosis and treatment. J Paediatr Child Health 2013; 49: 820–824.Google Scholar
7. Shargorodsky, M, Boaz, M, Pasternak, S, et al. Serum homocysteine, folate, vitamin B12 levels and arterial stiffness in diabetic patients: which of them is really important in atherogenesis? Diabetes Metab Res Rev 2009; 25: 70–75.Google Scholar
8. Dayal, S, Arning, E, Bottiglieri, T, et al. Cerebral vascular dysfunction mediated by superoxide in hyperhomocysteinemic mice. Stroke 2004; 35: 1957–1962.Google Scholar
9. Mahalle, N, Kulkarni, MV, Garg, MK, Naik, SS. Vitamin B12 deficiency and hyperhomocysteinemia as correlates of cardiovascular risk factors in Indian subjects with coronary artery disease. J Cardiol 2013; 61: 289–294.Google Scholar
10. Potter, K, Hankey, GJ, Green, DJ, Eikelboom, J, Jamrozik, K, Arnolda, LF. The effect of long-term homocysteine-lowering on carotid intima media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis. BMC Cardiovasc Disord 2008; 8: 24.Google Scholar
11. Zoccali, C, Bode-Boger, S, Mallamaci, F, et al. Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet 2001; 358: 2113–2117.Google Scholar
12. Schiro, A, Wilkinson, FL, Weston, R, Smyth, JV, Serracino-Inglott, F, Alexander, MY. Endothelial microparticles as conveyors of information in atherosclerotic disease. Atherosclerosis 2014; 234: 295–302.Google Scholar
13. Cooke, JP. Asymmetrical dimethylarginine: the Uber marker? Circulation 2004; 109: 1813–1818.Google Scholar
14. 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: 481–487.Google Scholar
15. Tain, YL, Huang, LT. Asymmetric dimethylarginine: clinical applications in pediatric medicine. J Formos Med Assoc 2011; 110: 70.Google Scholar
16. Zoccali, C, Mallamaci, F, Tripepi, G. Novel cardiovascular risk factors in end-stage renal disease. J Am Soc Nephrol 2004; 15: 77–80.Google Scholar
17. Visser, M, Paulus, WJ, Vermeulen, MA, et al. The role of asymmetric dimethylarginine and arginine in the failing heart and its vasculature. Eur J Heart Fail 2010; 12: 74–81.Google Scholar
18. Ayer, JG, Harmer, JA, Nakhla, S, et al. HDL-cholesterol, blood pressure, and asymmetric dimethylarginine are significantly associated with arterial wall thickness in children. Arterioscler Thromb Vasc Biol 2009; 296: 943–949.Google Scholar
19. Daniels, SR, Meyer, RA, Liang, Y, Bove, KE. Echocardiographically determined left ventricular mass index in normal children, adolescents and young adults. J Am Coll Cardiol 1988; 12: 703–708.Google Scholar
20. Day, TG, Park, M, Kinra, S. The association between blood pressure and carotid intima-media thickness in children: a systematic review. Cardiol Young 2017; 27: 1295–1305.Google Scholar
21. Schmidt, DE, Manca, M, Hoefer, IE. Circulating endothelial cells in coronary artery disease and acute coronary syndrome. Trends Cardiovasc Med 2015; 25: 578–587.Google Scholar
22. McCully, KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56: 111.Google Scholar
23. Potter, K, Hankey, GJ, Green, DJ, Eikelboom, J, Jamrozik, K, Arnolda, LF. The effect of long-term homocysteine-lowering on carotid intima media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis. BMC Cardiovasc Disord 2008; 8: 24.Google Scholar
24. Pawlak, R. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians? Am J Prev Med 2015; 48: e11–26.Google Scholar
25. Harker, LA, Ross, R, Slichter, SJ, Scott, CR. Homocysteine-induced arteriosclerosis: the role of endothelial cell injury and platelet response in its genesis. J Clin Invest 1976; 291: 731–741.Google Scholar
26. Mudd, SH, Levy, HL, Skovby, FD. Disorders of transsulfuration. In: Scriver C, Beaudet AL, Sly WS, Vale D (eds). The Metabolic Basis of Inherited Disease, 6th edn. New York, 1989: 693–734.Google Scholar
27. Pignoli, P, Tremoli, E, Poli, A, Oreste, P, Paoletti, R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation 1986; 74: 1399–1406.Google Scholar
28. Libetta, C, Villa, G, Pirrelli, S, et al. Homocysteine plasma levels correlate with intimal carotid artery thickness in haemodialysis patients. Nephrol Dial Transplant 2001; 16: 2444–2445.Google Scholar
29. Sabri, MR, Kelishadi, R. The thickness of the intimal and medial layers of the carotid arteries, and the index of left ventricular mass, in children of patients with premature coronary arterial disease. Cardiol Young 2007; 17: 609–616.Google Scholar
30. Daniels, SR, Meyer, RA, Liang, Y, Bove, KE. Echocardiographically determined left ventricular mass index in normal children, adolescents and young adults. J Am Coll Cardiol 1988; 12: 703–708.Google Scholar
31. Blacher, J, Demuth, K, Guerin, AP, et al. Association between plasma homocysteine concentrations and cardiac hypertrophy in end-stage renal disease. J Nephrol 1998; 18: 248–255.Google Scholar
32. Cordina, RL, Nakhla, S, Meagher, S, et al. Widespread endotheliopathy in adults with cyanotic congenital heart disease. Cardiol Young 2015; 25: 511–519.Google Scholar
33. Miyazaki, H, Matsuoka, H, Cooke, JP, et al. Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 1999; 99: 1141–1146.Google Scholar
34. Stühlinger, MC, Tsao, PS, Her, JH, et al. Homocysteine impairs the nitric oxide synthase pathway role of asymmetric dimethylarginine. Circulation 2001; 104: 2569–2575.Google Scholar