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Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance

  • Tom Teerlink
Published/Copyright: September 21, 2011
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 43 Issue 10

Abstract

Asymmetric dimethylarginine (ADMA) is a potent inhibitor of nitric oxide synthase and is regarded as a novel risk factor for cardiovascular disease. The metabolic pathways of ADMA and homocysteine are strongly intertwined. First, during synthesis of ADMA, two equivalents of homocysteine are formed. Second, homocysteine has been shown to inhibit the ADMA-degrading enzyme dimethylarginine dimethylaminohydrolase. Finally, homocysteine, either directly or by increasing oxidative stress, may promote release of free ADMA by accelerating protein degradation. Currently used techniques for the quantification of ADMA in plasma are mostly based on liquid chromatography with fluorimetric or mass spectrometric detection. Plasma ADMA has a very narrow concentration distribution, with an inter-individual coefficient of variation of approximately 12%, and even slightly elevated ADMA concentrations are associated with increased cardiovascular disease risk. Therefore, to generate useful results in clinical research, high precision of the assay used for the quantification of ADMA assay is a matter of prime importance. Assays with a high coefficient of variation may lead to low statistical power in clinical trials and to a severe underestimation of the strength of associations in epidemiological studies.

Keywords: asymmetric dimethylarginine; cardiovascular disease; endothelial dysfunction; homocysteine; nitric oxide
Corresponding author: Dr. T. Teerlink, Department of Clinical Chemistry, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands Phone: +31-204443872, Fax: +31-204443895,

References

1. 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; 339:572–5.10.1016/0140-6736(92)90865-ZSearch in Google Scholar

2. Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 2000; 20:2032–7.10.1161/01.ATV.20.9.2032Search in Google Scholar

3. Böger RH. Association of asymmetric dimethylarginine and endothelial dysfunction. Clin Chem Lab Med 2003; 41:1467–72.10.1515/CCLM.2003.225Search in Google Scholar

4. Zoccali C, Bode-Böger SM, Mallamaci F, Benedetto FA, Tripepi G, Malatino LS, et al. Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet 2001; 358:2113–7.10.1016/S0140-6736(01)07217-8Search in Google Scholar

5. Valkonen VP, Päivä H, Salonen JT, Lakka TA, Lehtimäki T, Laakso J, et al. Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet 2001; 358:2127–8.10.1016/S0140-6736(01)07184-7Search in Google Scholar

6. Gary JD, Clarke S. RNA and protein interactions modulated by protein arginine methylation. Prog Nucleic Acid Res Mol Biol 1998; 61:65–131.10.1016/S0079-6603(08)60825-9Search in Google Scholar

7. Boisvert FM, Côté J, Boulanger MC, Richard S. A proteomic analysis of arginine-methylated protein complexes. Mol Cell Proteomics 2003; 2:1319–30.10.1074/mcp.M300088-MCP200Search in Google Scholar PubMed

8. Bachand F, Silver PA. PRMT3 is a ribosomal protein methyltransferase that affects the cellular levels of ribosomal subunits. EMBO J 2004; 23:2641–50.10.1038/sj.emboj.7600265Search in Google Scholar PubMed PubMed Central

9. Miranda TB, Khusial P, Cook JR, Lee JH, Gunderson SI, Pestka S, et al. Spliceosome Sm proteins D1, D3, and B/B′ are asymmetrically dimethylated at arginine residues in the nucleus. Biochem Biophys Res Commun 2004; 323:382–7.10.1016/j.bbrc.2004.08.107Search in Google Scholar PubMed

10. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 2002; 82:373–428.10.1152/physrev.00027.2001Search in Google Scholar PubMed

11. Teerlink T. ADMA metabolism and clearance. Vasc Med 2005; 10:S73–81.10.1191/1358863x05vm597oaSearch in Google Scholar

12. Ogawa T, Kimoto M, Sasaoka K. Purification and properties of a new enzyme, NG,NG-dimethylarginine dimethylaminohydrolase, from rat kidney. J Biol Chem 1989; 264:10205–9.10.1016/S0021-9258(18)81786-0Search in Google Scholar

13. MacAllister RJ, Parry H, Kimoto M, Ogawa T, Russell RJ, Hodson H, et al. Regulation of nitric oxide synthesis by dimethylarginine dimethylaminohydrolase. Br J Pharmacol 1996; 119:1533–40.10.1111/j.1476-5381.1996.tb16069.xSearch in Google Scholar PubMed PubMed Central

14. Kimoto M, Tsuji H, Ogawa T, Sasaoka K. Detection of NG,NG-dimethylarginine dimethylaminohydrolase in the nitric oxide-generating systems of rats using monoclonal antibody. Arch Biochem Biophys 1993; 300:657–62.10.1006/abbi.1993.1091Search in Google Scholar PubMed

15. Tran CT, Fox MF, Vallance P, Leiper JM. Chromosomal localization, gene structure, and expression pattern of DDAH1: comparison with DDAH2 and implications for evolutionary origins. Genomics 2000; 68:101–5.10.1006/geno.2000.6262Search in Google Scholar PubMed

16. Leiper JM, Santa Maria J, Chubb A, MacAllister RJ, Charles IG, Whitley GS, et al. Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases. Biochem J 1999; 343:209–14.10.1042/bj3430209Search in Google Scholar

17. Achan V, Broadhead M, Malaki M, Whitley GS, Leiper J, MacAllister R, et al. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 2003; 23:1455–9.10.1161/01.ATV.0000081742.92006.59Search in Google Scholar PubMed

18. Cooke JP, Dzau VJ. Nitric oxide synthase: role in the genesis of vascular disease. Annu Rev Med 1997; 48:489–509.10.1146/annurev.med.48.1.489Search in Google Scholar PubMed

19. Cooke JP. Asymmetrical dimethylarginine: the Über marker? Circulation 2004; 109:1813–8.10.1161/01.CIR.0000126823.07732.D5Search in Google Scholar PubMed

20. 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 2001; 100:161–7.10.1042/cs1000161Search in Google Scholar

21. Ohike Y, Kozaki K, Iijima K, Eto M, Kojima T, Ohga E, et al. Amelioration of vascular endothelial dysfunction in obstructive sleep apnea syndrome by nasal continuous positive airway pressure. Possible involvement of nitric oxide and asymmetric NG,NG-dimethylarginine. Circ J 2005; 69:221–6.10.1253/circj.69.221Search in Google Scholar

22. Miyazaki H, Matsuoka H, Cooke JP, Usui M, Ueda S, Okuda S, et al. Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 1999; 99:1141–6.10.1161/01.CIR.99.9.1141Search in Google Scholar

23. Zoccali C, Benedetto FA, Maas R, Mallamaci F, Tripepi G, Malatino LS, et al. Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease. J Am Soc Nephrol 2002; 13:490–6.10.1681/ASN.V132490Search in Google Scholar

24. Lu TM, Ding YA, Lin SJ, Lee WS, Tai HC. Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention. Eur Heart J 2003; 24:1912–9.10.1016/j.ehj.2003.08.013Search in Google Scholar

25. Nijveldt RJ, Teerlink T, van der Hoven B, Siroen MP, Kuik DJ, Rauwerda JA, et al. Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality. Clin Nutr 2003; 22:23–30.10.1054/clnu.2002.0613Search in Google Scholar

26. Böger RH. The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor. Cardiovasc Res 2003; 59:824–33.10.1016/S0008-6363(03)00500-5Search in Google Scholar

27. Stühlinger MC, Stanger O. Asymmetric dimethyl-L-arginine (ADMA): a possible link between homocyst(e)ine and endothelial dysfunction. Curr Drug Metab 2005; 6:3–14.10.2174/1389200052997393Search in Google Scholar PubMed

28. Dayal S, Lentz SR. ADMA and hyperhomocysteinemia. Vasc Med 2005; 10:S27–33.10.1177/1358836X0501000105Search in Google Scholar

29. Stern F, Berner YN, Polyak Z, Komarnitsky M, Sela BA, Hopp M, et al. Homocysteine effect on protein degradation rates. Clin Biochem 2004; 37:1002–9.10.1016/j.clinbiochem.2004.07.011Search in Google Scholar PubMed

30. Stühlinger MC, Tsao PS, Her JH, Kimoto M, Balint RF, Cooke JP. Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine. Circulation 2001; 104:2569–75.10.1161/hc4601.098514Search in Google Scholar PubMed

31. Yi P, Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ. Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem 2000; 275:29318–23.10.1074/jbc.M002725200Search in Google Scholar

32. Ingrosso D, Cimmino A, Perna AF, Masella L, De Santo NG, De Bonis ML, et al. Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia. Lancet 2003; 361:1693–9.10.1016/S0140-6736(03)13372-7Search in Google Scholar

33. Böger RH, Sydow K, Borlak J, Thum T, Lenzen H, Schubert B, et al. LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ Res 2000; 87:99–105.10.1161/01.RES.87.2.99Search in Google Scholar

34. Bellamy MF, McDowell IF, Ramsey MW, Brownlee M, Bones C, Newcombe RG, et al. Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults. Circulation 1998; 98:1848–52.10.1161/01.CIR.98.18.1848Search in Google Scholar

35. Stühlinger MC, Oka RK, Graf EE, Schmölzer I, Upson BM, Kapoor O, et al. Endothelial dysfunction induced by hyperhomocyst(e)inemia. Role of asymmetric dimethylarginine. Circulation 2003; 108:933–8.10.1161/01.CIR.0000085067.55901.89Search in Google Scholar

36. Wanby P, Brattström L, Brudin L, Hultberg B, Teerlink T. Asymmetric dimethylarginine and total homocysteine in plasma after oral methionine loading. Scand J Clin Lab Invest 2003; 63:347–53.10.1080/00365510310002040Search in Google Scholar

37. Doshi S, McDowell I, Goodfellow J, Stabler S, Böger R, Allen R, et al. Relationship between S-adenosylmethionine, S-adenosylhomocysteine, asymmetric dimethylarginine, and endothelial function in healthy human subjects during experimental hyper- and hypohomocysteinemia. Metabolism 2005; 54:351–60.10.1016/j.metabol.2004.09.015Search in Google Scholar

38. Dierkes J, Westphal S, Luley C. Serum homocysteine increases after therapy with fenofibrate or bezafibrate. Lancet 1999; 354:219–20.10.1016/S0140-6736(99)02153-4Search in Google Scholar

39. Dierkes J, Westphal S, Martens-Lobenhoffer J, Luley C, Bode-Böger SM. Fenofibrate increases the L-arginine:ADMA ratio by increase of L-arginine concentration but has no effect on ADMA concentration. Atherosclerosis 2004; 173:239–44.10.1016/j.atherosclerosis.2003.12.004Search in Google Scholar PubMed

40. Holven KB, Haugstad TS, Holm T, Aukrust P, Ose L, Nenseter MS. Folic acid treatment reduces elevated plasma levels of asymmetric dimethylarginine in hyperhomocysteinaemic subjects. Br J Nutr 2003; 89:359–63.10.1079/BJN2002779Search in Google Scholar PubMed

41. Sydow K, Schwedhelm E, Arakawa N, Bode-Böger SM, Tsikas D, Hornig B, et al. ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia: effects of L-arginine and B vitamins. Cardiovasc Res 2003; 57:244–52.10.1016/S0008-6363(02)00617-XSearch in Google Scholar

42. Ziegler S, Mittermayer F, Plank C, Minar E, Wolzt M, Schernthaner GH. Homocyst(e)ine-lowering therapy does not affect plasma asymmetrical dimethylarginine concentrations in patients with peripheral artery disease. J Clin Endocrinol Metab 2005; 90:2175–8.10.1210/jc.2004-1087Search in Google Scholar

43. Böger RH, Bode-Böger SM, Sydow K, Heistad DD, Lentz SR. Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia. Arterioscler Thromb Vasc Biol 2000; 20:1557–64.10.1161/01.ATV.20.6.1557Search in Google Scholar

44. Kielstein JT, Böger RH, Bode-Böger SM, Frölich JC, Haller H, Ritz E, et al. Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J Am Soc Nephrol 2002; 13:170–6.10.1681/ASN.V131170Search in Google Scholar

45. Yoo JH, Lee SC. Elevated levels of plasma homocyst(e)ine and asymmetric dimethylarginine in elderly patients with stroke. Atherosclerosis 2001; 158:425–30.10.1016/S0021-9150(01)00444-0Search in Google Scholar

46. Selley ML. Increased concentrations of homocysteine and asymmetric dimethylarginine and decreased concentrations of nitric oxide in the plasma of patients with Alzheimer' disease. Neurobiol Aging 2003; 24:903–7.10.1016/S0197-4580(03)00007-1Search in Google Scholar

47. Jonasson TF, Hedner T, Hultberg B, Öhlin H. Hyperhomocysteinaemia is not associated with increased levels of asymmetric dimethylarginine in patients with ischaemic heart disease. Eur J Clin Invest 2003; 33:543–9.10.1046/j.1365-2362.2003.01184.xSearch in Google Scholar

48. Lu TM, Ding YA, Leu HB, Yin WH, Sheu WH, Chu KM. Effect of rosuvastatin on plasma levels of asymmetric dimethylarginine in patients with hypercholesterolemia. Am J Cardiol 2004; 94:157–61.10.1016/j.amjcard.2004.03.052Search in Google Scholar

49. Mooy JM, Grootenhuis PA, de Vries H, Valkenburg HA, Bouter LM, Kostense PJ, et al. Prevalence and determinants of glucose intolerance in a Dutch Caucasian population. The Hoorn Study. Diabetes Care 1995; 18:1270–3.10.2337/diacare.18.9.1270Search in Google Scholar

50. Chen BM, Xia LW, Zhao RQ. Determination of N(G),N(G)-dimethylarginine in human plasma by high-performance liquid chromatography. J Chromatogr B 1997; 692:467–71.10.1016/S0378-4347(96)00531-2Search in Google Scholar

51. Pettersson A, Uggla L, Backman V. Determination of dimethylated arginines in human plasma by high-performance liquid chromatography. J Chromatogr B 1997; 692:257–62.10.1016/S0378-4347(96)00525-7Search in Google Scholar

52. Tsikas D, Junker W, Frölich JC. Determination of dimethylated arginines in human plasma by high-performance liquid chromatography. J Chromatogr B 1998; 705:174–6.Search in Google Scholar

53. Pi J, Kumagai Y, Sun G, Shimojo N. Improved method for simultaneous determination of L-arginine and its mono- and dimethylated metabolites in biological samples by high-performance liquid chromatography. J Chromatogr B 2000; 742:199–203.10.1016/S0378-4347(00)00145-6Search in Google Scholar

54. Chen BM, Xia LW, Liang SX, Chen GH, Deng FL, Zhang WR, et al. Simultaneous determination of L-arginine and dimethylarginines in human urine by high-performance liquid chromatography. Anal Chim Acta 2001; 444:223–7.10.1016/S0003-2670(01)01211-9Search in Google Scholar

55. Teerlink T, Nijveldt RJ, de Jong S, van Leeuwen PA. Determination of arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in human plasma and other biological samples by high-performance liquid chromatography. Anal Biochem 2002; 303:131–7.10.1006/abio.2001.5575Search in Google Scholar

56. Zhang WZ, Kaye DM. Simultaneous determination of arginine and seven metabolites in plasma by reversed-phase liquid chromatography with a time-controlled ortho-phthaldialdehyde precolumn derivatization. Anal Biochem 2004; 326:87–92.10.1016/j.ab.2003.11.006Search in Google Scholar

57. Teerlink T. Determination of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine in biological samples by HPLC. Methods Mol Med 2005; 108:263–74.Search in Google Scholar

58. Ueno S, Sano A, Kotani K, Kondoh K, Kakimoto Y. Distribution of free methylarginines in rat tissues and in the bovine brain. J Neurochem 1992; 59:2012–6.10.1111/j.1471-4159.1992.tb10088.xSearch in Google Scholar

59. Park KS, Lee HW, Hong SY, Shin S, Kim S, Paik WK. Determination of methylated amino acids in human serum by high-performance liquid chromatography. J Chromatogr 1988; 440:225–30.10.1016/S0021-9673(00)94526-6Search in Google Scholar

60. Marra M, Bonfigli AR, Testa R, Testa I, Gambini A, Coppa G. High-performance liquid chromatographic assay of asymmetric dimethylarginine, symmetric dimethylarginine, and arginine in human plasma by derivatization with naphthalene-2,3-dicarboxaldehyde. Anal Biochem 2003; 318:13–7.10.1016/S0003-2697(03)00157-XSearch in Google Scholar

61. Heresztyn T, Worthley MI, Horowitz JD. Determination of L-arginine and NG,NG- and NG,NG′-dimethyl-L-arginine in plasma by liquid chromatography as AccQ-Fluor(TM) fluorescent derivatives. J Chromatogr B 2004; 805:325–9.10.1016/j.jchromb.2004.03.020Search in Google Scholar PubMed

62. Nonaka S, Tsunoda M, Imai K, Funatsu T. High-performance liquid chromatographic assay of NG-monomethyl-L-arginine, NG,NG-dimethyl-L-arginine, and NG,NG′-dimethyl-L-arginine using 4-fluoro-7-nitro-2,1,3-benzoxa-diazole as a fluorescent reagent. J Chromatogr A 2005; 1066:41–5.10.1016/j.chroma.2005.01.052Search in Google Scholar PubMed

63. Caussé E, Siri N, Arnal JF, Bayle C, Malatray P, Valdiguié P, et al. Determination of asymmetrical dimethylarginine by capillary electrophoresis-laser-induced fluorescence. J Chromatogr B 2000; 741:77–83.10.1016/S0378-4347(00)00034-7Search in Google Scholar

64. Trapp G, Sydow K, Dulay MT, Chou T, Cooke JP, Zare RN. Capillary electrophoretic and micellar electrokinetic separations of asymmetric dimethyl-L-arginine and structurally related amino acids: quantitation in human plasma. J Sep Sci 2004; 27:1483–90.10.1002/jssc.200401918Search in Google Scholar

65. Tsikas D, Schubert B, Gutzki FM, Sandmann J, Frölich JC. Quantitative determination of circulating and urinary asymmetric dimethylarginine (ADMA) in humans by gas chromatography-tandem mass spectrometry as methyl ester tri(N-pentafluoropropionyl) derivative. J Chromatogr B 2003; 798:87–99.10.1016/j.jchromb.2003.09.001Search in Google Scholar

66. Albsmeier J, Schwedhelm E, Schulze F, Kastner M, Böger RH. Determination of NG,NG-dimethyl-L-arginine, an endogenous NO synthase inhibitor, by gas chromatography-mass spectrometry. J Chromatogr B 2004; 809:59–65.10.1016/j.jchromb.2004.06.008Search in Google Scholar

67. Vishwanathan K, Tackett RL, Stewart JT, Bartlett MG. Determination of arginine and methylated arginines in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B 2000; 748:157–66.10.1016/S0378-4347(00)00399-6Search in Google Scholar

68. Martens-Lobenhoffer J, Bode-Böger SM. Simultaneous detection of arginine, asymmetric dimethylarginine, symmetric dimethylarginine and citrulline in human plasma and urine applying liquid chromatography-mass spectrometry with very straightforward sample preparation. J Chromatogr B 2003; 798:231–9.10.1016/j.jchromb.2003.09.050Search in Google Scholar PubMed

69. Kirchherr H, Kühn-Velten WN. HPLC-tandem mass spectrometric method for rapid quantification of dimethylarginines in human plasma. Clin Chem 2005; 51:249–52.10.1373/clinchem.2004.042663Search in Google Scholar PubMed

70. Martens-Lobenhoffer J, Krug O, Bode-Böger SM. Determination of arginine and asymmetric dimethylarginine (ADMA) in human plasma by liquid chromatography/mass spectrometry with the isotope dilution technique. J Mass Spectrom 2004; 39:1287–94.10.1002/jms.684Search in Google Scholar PubMed

71. Schwedhelm E, Tan-Andresen J, Maas R, Riederer U, Schulze F, Böger RH. Liquid chromatography-tandem mass spectrometry method for the analysis of asymmetric dimethylarginine in human plasma. Clin Chem 2005; 51:1268–71.10.1373/clinchem.2004.046037Search in Google Scholar PubMed

72. Schulze F, Wesemann R, Schwedhelm E, Sydow K, Albsmeier J, Cooke JP, et al. Determination of asymmetric dimethylarginine (ADMA) using a novel ELISA assay. Clin Chem Lab Med 2004; 42:1377–83.10.1515/CCLM.2004.257Search in Google Scholar PubMed

73. Schwedhelm E. Quantification of ADMA: analytical approaches. Vasc Med 2005; 10:S89–95.10.1177/1358836X0501000113Search in Google Scholar PubMed

74. Teerlink T, Neele SJ, de Jong S, Netelenbos JC, Stehouwer CD. Oestrogen replacement therapy lowers plasma levels of asymmetrical dimethylarginine in healthy postmenopausal women. Clin Sci 2003; 105:67–71.10.1042/CS20020309Search in Google Scholar PubMed

75. Post MS, Verhoeven MO, van der Mooren MJ, Kenemans P, Stehouwer CD, Teerlink T. Effect of hormone replacement therapy on plasma levels of the cardiovascular risk factor asymmetric dimethylarginine: a randomized, placebo-controlled 12-week study in healthy early postmenopausal women. J Clin Endocrinol Metab 2003; 88:4221–6.10.1210/jc.2003-030584Search in Google Scholar PubMed

Published Online: 2011-9-21
Published in Print: 2005-10-1

©2005 by Walter de Gruyter Berlin New York

Articles in the same Issue

  1. Homocysteine research – where do we stand and where are we going?
  2. Hyperhomocysteinemia and arteriosclerosis: historical perspectives
  3. Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
  4. Homocysteine and vascular disease in diabetes: a double hit?
  5. Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
  6. Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
  7. Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
  8. Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
  9. Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
  10. Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
  11. Hyperhomocysteinemia and macromolecule modifications in uremic patients
  12. Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
  13. Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
  14. Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
  15. Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
  16. A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
  17. Betaine: a key modulator of one-carbon metabolism and homocysteine status
  18. Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
  19. Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
  20. Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
  21. Homocysteine and B vitamins in mild cognitive impairment and dementia
  22. Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
  23. Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
  24. Homocysteine – a newly recognised risk factor for osteoporosis
  25. Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
  26. Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
  27. Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
  28. Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
  29. Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
  30. Interactions between folate and aging for carcinogenesis
  31. The potential cocarcinogenic effect of vitamin B12 deficiency
  32. The vegetarian lifestyle and DNA methylation
https://doi.org/10.1515/CCLM.2005.197
Keywords for this article
asymmetric dimethylarginine; cardiovascular disease; endothelial dysfunction; homocysteine; nitric oxide

Articles in the same Issue

  1. Homocysteine research – where do we stand and where are we going?
  2. Hyperhomocysteinemia and arteriosclerosis: historical perspectives
  3. Homocysteine and heart failure: a review of investigations from the Framingham Heart Study
  4. Homocysteine and vascular disease in diabetes: a double hit?
  5. Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia
  6. Effects of homocysteine on vascular and tissue adenosine: a stake in homocysteine pathogenicity?
  7. Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
  8. Carotid narrowing degree and plasma thiol levels in carotid endarterectomy patients
  9. Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy
  10. Hyperhomocysteinaemia in chronic kidney disease: focus on transmethylation
  11. Hyperhomocysteinemia and macromolecule modifications in uremic patients
  12. Hyperhomocysteinemia and response of methionine cycle intermediates to vitamin treatment in renal patients
  13. Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population
  14. Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects
  15. Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project
  16. A laboratory algorithm with homocysteine as the primary parameter reduces the cost of investigation of folate and cobalamin deficiency
  17. Betaine: a key modulator of one-carbon metabolism and homocysteine status
  18. Molecular targeting by homocysteine: a mechanism for vascular pathogenesis
  19. Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
  20. Homocysteine in relation to cognitive performance in pathological and non-pathological conditions
  21. Homocysteine and B vitamins in mild cognitive impairment and dementia
  22. Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study
  23. Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions
  24. Homocysteine – a newly recognised risk factor for osteoporosis
  25. Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women
  26. Elevated levels of asymmetric dimethylarginine (ADMA) as a marker of cardiovascular disease and mortality
  27. Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance
  28. Concentrations of homocysteine, related metabolites and asymmetric dimethylarginine in preeclamptic women with poor nutritional status
  29. Asymmetric dimethylarginine, homocysteine and renal function – is there a relation?
  30. Interactions between folate and aging for carcinogenesis
  31. The potential cocarcinogenic effect of vitamin B12 deficiency
  32. The vegetarian lifestyle and DNA methylation
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