Homoarginine in the shadow of asymmetric dimethylarginine: from nitric oxide to cardiovascular disease

Amino Acids

Volumn 47, Issue 9, 2015, Pages 1741-1750

  Papageorgiou, Nikolaos ^a   Androulakis, Emmanuel ^a   Papaioannou, Spyridon ^a   Antoniades, Charalambos ^a   Tousoulis, Dimitris ^a  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

Author keywords

ADMA Asymmetric dimethylarginine; AGAT Arginineglycine amidinotransferase; CAD Coronary artery disease; CVD Cardiovascular disease; DDAH Dimethylarginine dimethylaminohydrolase; eNOS Endothelial nitric oxide synthase; FMD Flow mediated dilatation; GAMT Guanidinoacetate methyltransferase; hArg Homoarginine; IMT Intima media thickness; MMA Monomethylarginine; nNOS Neuronal nitric oxide synthase; NO Nitric oxide; NOS NO synthase; PCI Percutaneous coronary intervention; PRMTs Protein arginine N methyltransferases; ROS Reactive oxygen species; SDMA Symmetric dimethylarginine

Indexed keywords

ARGININE; HOMOARGININE; N(G),N(G) DIMETHYLARGININE; NITRIC OXIDE; AMIDINOTRANSFERASE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; GLYCINE AMIDINOTRANSFERASE; N,N-DIMETHYLARGININE; NOS3 PROTEIN, HUMAN;

AMINO ACID BLOOD LEVEL; AMINO ACID METABOLISM; AMINO ACID SYNTHESIS; ARTICLE; ATHEROGENESIS; ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; CORONARY ARTERY DISEASE; DIASTOLIC DYSFUNCTION; DRUG EFFECT; ENDOTHELIAL DYSFUNCTION; HEART FAILURE; HEART INFARCTION; HUMAN; NONHUMAN; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PERIPHERAL OCCLUSIVE ARTERY DISEASE; PRIORITY JOURNAL; PROGNOSIS; SINGLE NUCLEOTIDE POLYMORPHISM; SUDDEN CARDIAC DEATH; SUPPLEMENTATION; TAKOTSUBO CARDIOMYOPATHY; ANALOGS AND DERIVATIVES; ANIMAL; BLOOD; METABOLISM; PATHOLOGY; VASCULAR ENDOTHELIUM;

AMIDINOTRANSFERASES; ANIMALS; ARGININE; ATHEROSCLEROSIS; ENDOTHELIUM, VASCULAR; HOMOARGININE; HUMANS; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III;

EID: 84940462137     PISSN: 09394451     EISSN: 14382199     Source Type: Journal    
DOI: 10.1007/s00726-015-2017-y     Document Type: Article

References (69)

1. Achan V, Broadhead M, Malaki M et al (2003) Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 23:1455-1459
2. Antoniades C, Tousoulis D, Marinou K et al (2006) Asymmetrical dimethylarginine regulates endothelial function in methionine-induced but not in chronic homocystinemia in humans: effect of oxidative stress and proinflammatory cytokines. Am J Clin Nutr 84:781-788
3. Atzler D, Rosenberg M, Anderssohn M et al (2013) Homoarginine-an independent marker of mortality in heart failure. Int J Cardiol 168:4907-4909
4. Atzler D, Gore MO, Ayers CR et al (2014) Homoarginine and cardiovascular outcome in the population-based Dallas Heart Study. Arterioscler Thromb Vasc Biol 34:2501-2507
5. Böger RH (2003) The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor. Cardiovasc Res 59:824-833
6. Böger RH (2005) Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials. Vasc Med 10(Suppl 1):S19-S25
7. Böger RH, Sydow K, Borlak J et al (2000) LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ Res 87:99-105
8. Bonetti PO, Lerman LO, Lerman A (2003) Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 23:168-175
9. Bulau P, Zakrzewicz D, Kitowska K et al (2007) Analysis of methylarginine metabolism in the cardiovascular system identifies the lung as a major source of ADMA. Am J Physiol Lung Cell Mol Physiol 2007(292):L18-L24
10. Cavusoglu E, Ruwende C, Chopra V et al (2009) Relationship of baseline plasma ADMA levels to cardiovascular outcomes at 2 years in men with acute coronary syndrome referred for coronary angiography. Coron Artery Dis 20:112-117
11. Chen PY, Sanders PW (1993) Role of nitric oxide synthesis in salt-sensitive hypertension in Dahl/Rapp rats. Hypertension 22:812-818
12. Choe CU, Atzler D, Wild PS et al (2013) Homoarginine levels are regulated by l-arginine:glycine amidinotransferase and affect stroke outcome: results from human and murine studies. Circulation 128:1451-1461
13. Davids M, Ndika JD, Salomons GS, Blom HJ, Teerlink T (2012) Promiscuous activity of arginine:glycine amidinotransferase is responsible for the synthesis of the novel cardiovascular risk factor homoarginine. FEBS Lett 586:3653-3657
14. Drechsler C, Kollerits B, Meinitzer A et al (2013) Homoarginine and progression of chronic kidney disease: results from the Mild to Moderate Kidney Disease Study. PLoS One 8:e63560
15. Fard A, Tuck CH, Donis JA et al (2000) Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 20:2039-2044
16. Fujiwara N, Osanai T, Kamada T et al (2000) Study on the relationship between plasma nitrite and nitrate level and salt sensitivity in human hypertension:modulation of nitric oxide synthesis by salt intake. Circulation 101:856-861
17. Furuki K, Adachi H, Matsuoka H et al (2007) Plasma levels of asymmetric dimethylarginine (ADMA) are related to intima-media thickness of the carotid artery: an epidemiological study. Atherosclerosis 191:206-210
18. Guzik TJ, Sadowski J, Kapelak B et al (2004) Systemic regulation of vascular NAD(P)H oxidase activity and nox isoform expression in human arteries and veins. Arterioscler Thromb Vasc Biol 24:1614-1620
19. Hori T, Matsubara T, Ishibashi T et al (2003) Significance of asymmetric dimethylarginine (ADMA) concentrations during coronary circulation in patients with vasospastic angina. Circ J 67:305-311
20. Huynh NN, Chin-Dusting J (2006) Amino acids, arginase and nitric oxide in vascular health. Clin Exp Pharmacol Physiol 33:1-8
21. Ito A, Tsao PS, Adimoolam S et al (1999) Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 99:3092-3095
22. Jaźwińska-Kozuba A, Martens-Lobenhoffer J, Kruszelnicka O et al (2013) Opposite associations of plasma homoarginine and ornithine with arginine in healthy children and adolescents. Int J Mol Sci 14:21819-21832
23. Juonala M, Viikari JS, Alfthan G et al (2007) Brachial artery flowmediated dilation and asymmetrical dimethylarginine in the cardiovascular risk in young Finns study. Circulation 116:1367-1373
24. Kaito K, Otsubo H, Usui N et al (2005) Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia. Br J Haematol 128:698-702
25. Kayacelebi AA, Pham VV, Willers J et al (2014a) Plasma homoarginine (hArg) and asymmetric dimethylarginine (ADMA) in patients with rheumatoid arthritis: is homoarginine a cardiovascular corrective in rheumatoid arthritis, an anti-ADMA? Int J Cardiol 176:1129-1131
26. Kayacelebi AA, Nguyen TH, Neil C, Horowitz JD, Jordan J, Tsikas D (2014b) Homoarginine and 3-nitrotyrosine in patients with Takotsubo cardiomyopathy. Int J Cardiol 173:546-547
27. Kielstein A, Tsikas D, Galloway GP, Mendelson JE (2007) Asymmetric dimethylarginine (ADMA)-a modulator of nociception in opiate tolerance and addiction? Nitric Oxide 17:55-59
28. Kleber ME, Seppälä I, Pilz S et al (2013) Genome-wide association study identifies 3 genomic loci significantly associated with serum levels of homoarginine: the Athero Remo Consortium. Circ Cardiovasc Genet 6:505-513
29. Krempl TK, Maas R, Sydow K, Meinertz T, Böger RH, Kahler J (2005) Elevation of asymmetric dimethylarginine in patients with unstable angina and recurrent cardiovascular events. Eur Heart J 26:1846-1851
30. Krzyzanowska K, Mittermayer F, Wolzt M, Schernthaner G (2007) Asymmetric dimethylarginine predicts cardiovascular events in patients with type 2 diabetes. Diabetes Care 30:1834-1839
31. Leiper JM, Santa Maria J, Chubb A et al (1999) Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases. Biochem J 343:209-214
32. Lenzen H, Tsikas D, Böger RH (2006) Asymmetric dimethylarginine (ADMA) and the risk for coronary heart disease: the multicenter CARDIAC Study. Eur J Clin Pharmacol 62(Suppl 1):45-49
33. Leong T, Zylberstein D, Graham I et al (2008) Asymmetric dimethylarginine independently predicts fatal and nonfatal myocardial infarction and stroke in women: 24-year follow-up of the population study of women in Gothenburg. Arterioscler Thromb Vasc Biol 28:961-967
34. Lu TM, Ding YA, Lin SJ, Lee WS, Tai HC (2003a) Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention. Eur Heart J 24:1912-1919
35. Lu TM, Ding YA, Charng MJ, Lin SJ (2003b) Asymmetrical dimethylarginine: a novel risk factor for coronary artery disease. Clin Cardiol 26:458-464
36. Maas R, Quitzau K, Schwedhelm E et al (2007) Asymmetrical dimethylarginine (ADMA) and coronary endothelial function in patients with coronary artery disease and mild hypercholesterolemia. Atherosclerosis 191:211-219
37. März W, Meinitzer A, Drechsler C et al (2010) Homoarginine, cardiovascular risk, and mortality. Circulation 122:967-975
38. Meinitzer A, Seelhorst U, Wellnitz B et al (2007) Asymmetrical dimethylarginine independently predicts total and cardiovascular mortality in individuals with angiographic coronary artery disease (the Ludwigshafen Risk and Cardiovascular Health Study). Clin Chem 53:273-283
39. Michel T (2013) R is for arginine: metabolism of arginine takes off again, in new directions. Circulation 128:1400-1404
40. Mittermayer F, Krzyzanowska K, Exner M et al (2006) Asymmetric dimethylarginine predicts major adverse cardiovascular events in patients with advanced peripheral artery disease. Arterioscler Thromb Vasc Biol 26:2536-2540
41. Miyazaki H, Matsuoka H, Cooke JP et al (1999) Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 99:1141-1146
42. Nicholls SJ, Wang Z, Koeth R et al (2007) Metabolic profiling of arginine and nitric oxide pathways predicts hemodynamic abnormalities and mortality in patients with cardiogenic shock after acute myocardial infarction. Circulation 116:2315-2324
43. Perticone F, Sciacqua A, Maio R et al (2005) Asymmetric dimethylarginine, l-arginine, and endothelial dysfunction in essential hypertension. J Am Coll Cardiol 46:518-523
44. Pilz S, Meinitzer A, Tomaschitz A et al (2011a) Low homoarginine concentration is a novel risk factor for heart disease. Heart 97:1222-1227
45. Pilz S, Tomaschitz A, Meinitzer A et al (2011b) Low serum homoarginine is a novel risk factor for fatal strokes in patients undergoing coronary angiography. Stroke 42:1132-1134
46. Pilz S, Edelmann F, Meinitzer A et al (2014) Associations of methylarginines and homoarginine with diastolic dysfunction and cardiovascular risk factors in patients with preserved left ventricular ejection fraction. J Card Fail 20:923-930
47. Potena L, Fearon WF, Sydow K et al (2008) Asymmetric dimethylarginine and cardiac allograft vasculopathy progression: modulation by sirolimus. Transplantation 85:827-833
48. Radomski MW, Palmer RM, Moncada S (1990) An l-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci 87:5193-5197
49. Ross R (1999) Atherosclerosis - an inflammatory disease. N Engl J Med 340:115-126
50. Saarelainen H, Valtonen P, Punnonen K et al (2008) Subtle changes in ADMA and l-arginine concentrations in normal pregnancies are unlikely to account for pregnancy-related increased flow-mediated dilatation. Clin Physiol Funct Imaging 28:120-124
51. Schnabel R, Blankenberg S, Lubos E et al (2005) Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study. Circ Res 97:e53-e59
52. Schulze F, Lenzen H, Hanefeld C et al (2006) 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 152:493.e1-493.e8
53. Schwedhelm E, Wallaschofski H, Atzler D, et al. (2014) Incidence of all-cause and cardiovascular mortality predicted by symmetric dimethylarginine in the population-based study of health in Pomerania. PLoS One 9(5):e96875
54. Selcuk MT, Selcuk H, Temizhan A et al (2007) Asymmetric dimethylarginine plasma concentrations and l-arginine/asymmetric dimethylarginine ratio in patients with slow coronary flow. Coron Artery Dis 18:545-551
55. Sobczak A, Prokopowicz A, Radek M et al (2014) Tobacco smoking decreases plasma concentration of the emerging cardiovascular risk marker, l-homoarginine. Circ J 78:1254-1258
56. Tousoulis D, Koutsogiannis M, Papageorgiou N et al (2010) Endothelial dysfunction: potential clinical implications. Minerva Med 101:271-284
57. Tousoulis D, Bouras G, Antoniades C et al (2011a) Methionine-induced homocysteinemia impairs endothelial function in hypertensives: the role of asymmetrical dimethylarginine and antioxidant vitamins. Am J Hypertens 24:936-942
58. Tousoulis D, Kampoli AM, Papageorgiou N et al (2011b) Pathophysiology of atherosclerosis: the role of inflammation. Curr Pharm Des 17:4089-4110
59. Tousoulis D, Psaltopoulou T, Androulakis E et al (2015) Oxidative stress and early atherosclerosis: novel antioxidant treatment. Cardiovasc Drugs Ther 29:75-88
60. Tran CT, Leiper JM, Vallance P (2003) The DDAH/ADMA/NOS pathway. Atheroscler Suppl 4:33-40
61. Tsikas D, Kayacelebi AA (2014) Do homoarginine and asymmetric dimethylarginine act antagonistically in the cardiovascular system? Circ J 78:2094-2095
62. Tsikas D, Böger RH, Sandmann J, Bode-Böger SM, Frölich JC (2000a) Endogenous nitric oxide synthase inhibitors are responsible for the l-arginine paradox. FEBS Lett 478:1-3
63. Tsikas D, Sandmann J, Savva A et al (2000b) Assessment of nitric oxide synthase activity in vitro and in vivo by gas chromatography-mass spectrometry. J Chromatogr 742:143-153
64. Valkonen VP, Paiva H, Salonen JT et al (2001) Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet 358:2127-2128
65. Vallance P, Leone A, Calver A, Collier J, Moncada S (1992) Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339:572-575
66. Valtonen P, Laitinen T, Lyyra-Laitinen T et al (2008) Serum l-homoarginine concentration is elevated during normal pregnancy and is related to flow-mediated vasodilatation. Circ J 72:1879-1884
67. van der Zwan LP, Davids M, Scheffer PG, Dekker JM, Stehouwer CD, Teerlink T (2013) l-Homoarginine and l-arginine are antagonistically related to blood pressure in an elderly population: the Hoorn Study. J Hypertens 31:1114-1123
68. Vogl L, Pohlhammer J, Meinitzer A et al (2015) Serum concentrations of l-arginine and l-homoarginine in male patients with intermittent claudication: a cross-sectional and prospective investigation in the CAVASIC Study. Atherosclerosis 239:607-614
69. Zoccali C, Bode-Böger S, Mallamaci F et al (2001) Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet 358:2113-2117