Asymmetric dimethylarginine: A possible link between vascular disease and dementia

Current Alzheimer Research

Volumn 10, Issue 4, 2013, Pages 347-356

  Asif, Muhammad ^a   Soiza, Roy Louis ^b,c   McEvoy, Mark ^d   Mangoni, Arduino A ^b,c  

^a ROYAL CORNHILL HOSPITAL   (United Kingdom)

^b UNIVERSITY OF ABERDEEN   (United Kingdom)

^c WOODEND HOSPITAL   (United Kingdom)

^d UNIVERSITY OF NEWCASTLE   (Australia)

Author keywords

Alzheimer's disease; Asymmetric dimethylarginine; Dementia; Endothelium; Nitric oxide; Vascular disease

Indexed keywords

6 N,N' DIMETHYLARGININE; ACETYLSALICYLIC ACID; ARGININE; ATORVASTATIN; CONJUGATED ESTROGEN; ENDOTHELIAL NITRIC OXIDE SYNTHASE; ESTRADIOL; N(G) METHYLARGININE; N(G),N(G) DIMETHYLARGININE; PERINDOPRIL; PIOGLITAZONE; ROSIGLITAZONE; SIMVASTATIN; TELMISARTAN;

ATHEROSCLEROSIS; BLOOD VESSEL INJURY; BRAIN BLOOD FLOW; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; COGNITIVE DEFECT; DEMENTIA; DISEASE COURSE; ENDOTHELIAL DYSFUNCTION; ENZYME INHIBITION; ENZYME SYNTHESIS; HUMAN; LIFE EXPECTANCY; NEUROPROTECTION; NONHUMAN; OUTCOME ASSESSMENT; OXIDATIVE STRESS; PREDICTION; PREVALENCE; PRIORITY JOURNAL; REVIEW; SURVIVAL; VASCULAR DISEASE; VASOCONSTRICTION;

ARGININE; BRAIN; DEMENTIA; ENDOTHELIUM; ENZYME INHIBITORS; HUMANS; NEUROPROTECTIVE AGENTS; NITRIC OXIDE; OXIDATIVE STRESS; RISK FACTORS; VASCULAR DISEASES;

EID: 84878623996     PISSN: 15672050     EISSN: 18755828     Source Type: Journal    
DOI: 10.2174/1567205011310040001     Document Type: Review

References (90)

1. Mungas D, Reed BR, Ellis WG, Jagust WJ. The effects of age on rate of progression of Alzheimer disease and dementia with associated cerebrovascular disease. Arch Neurol 58(8): 1243-1247 (2001).
2. World Alzheimer Report 2010: the global economic impact of dementia. Alzheimer's Disease International 1-56 (2010).
3. Ledesma MD, Dotti CG. Peripheral cholesterol, metabolic disorders and Alzheimer's disease. Front Biosci (Elite Ed) 4: 181-194 (2012).
4. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, et al. Heart disease and stroke statistics-2011 update: a report from the American Heart Association. Circulation 123(4): e18-e209 (2011).
5. Brayne C. The elephant in the room-healthy brains in later life, epidemiology and public health. Nat Rev Neurosci 8(3): 233-239 (2007).
6. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. Forecasting the global burden of Alzheimer's disease. Alzheimers Dement 3(3): 186-191 (2007).
7. Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health 88(9): 1337-1342 (1998).
8. Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology 64(2): 277-281 (2005).
9. Vallance P, Leiper J. Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol 24(6): 1023-1030 (2004).
10. Cooke JP. ADMA: its role in vascular disease. Vasc Med 10(1): S11-S17 (2005).
11. Sibal L, Agarwal SC, Home PD, Boger RH. The Role of Asymmetric Dimethylarginine (ADMA) in Endothelial Dysfunction and Cardiovascular Disease. Curr Cardiol Rev 6(2): 82-90 (2010).
12. Cavalieri M, Enzinger C, Petrovic K, Pluta-Fuerst A, Homayoon N, Schmidt H, et al. Vascular dementia and Alzheimer's disease-are we in a dead-end road? Neurodegener Dis 7(1-3): 122-126 (2010).
13. Emanuele E, Martinelli V, Abbiati V, Ricevuti G. Linking atherosclerosis to Alzheimer's disease: focus on biomarkers. Front Biosci (Elite Ed) 4: 700-710 (2012).
14. de la Torre JC. Alzheimer disease as a vascular disorder: nosological evidence. Stroke 33(4): 1152-1162 (2002).
15. Knopman DS. Cerebrovascular disease and dementia. Br J Radiol 80 Spec No 2: S121-S127 (2007).
16. Viswanathan A, Rocca WA, Tzourio C. Vascular risk factors and dementia: how to move forward? Neurology 72(4): 368-374 (2009).
17. Qiu C, Xu W, Winblad B, Fratiglioni L. Vascular risk profiles for dementia and Alzheimer's disease in very old people: a populationbased longitudinal study. J Alzheimers Dis 20(1): 293-300 (2010).
18. in't Veld BA, Ruitenberg A, Hofman A, Stricker BH, Breteler MM. Antihypertensive drugs and incidence of dementia: the Rotterdam Study. Neurobiol Aging 22(3): 407-412 (2001).
19. Johnson KA, Albert MS. Perfusion abnormalities in prodromal AD. Neurobiol Aging 21(2): 289-292 (2000).
20. Petrovitch H, White LR, Izmirilian G, Ross GW, Havlik RJ, Markesbery W, et al. Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS. Honolulu-Asia aging Study. Neurobiol Aging 21(1): 57-62 (2000).
21. Bian K, Murad F. Nitric oxide (NO)-biogeneration, regulation, and relevance to human diseases. Front Biosci 8: d264-d278 (2003).
22. Schulz R, Rassaf T, Massion PB, Kelm M, Balligand JL. Recent advances in the understanding of the role of nitric oxide in cardiovascular homeostasis. Pharmacol Ther 108(3): 225-256 (2005).
23. Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AM. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci 8(10): 766-775 (2007).
24. Lamas S, Marsden PA, Li GK, Tempst P, Michel T. Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform. Proc Natl Acad Sci U S A 89(14): 6348-6352 (1992).
25. Forstermann U, Pollock JS, Nakane M. Nitric oxide synthases in the cardiovascular system. Trends Cardiovasc Med 3(3): 104-110 (1993).
26. Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J 33(7): 829-837d (2012).
27. Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 9(12): 1498-1505 (2003).
28. Csonka C, Szilvassy Z, Fulop F, Páli T, Blasig IE, Tosaki A, et al. Classic preconditioning decreases the harmful accumulation of nitric oxide during ischemia and reperfusion in rat hearts. Circulation 100(22): 2260-2266 (1999).
29. Umans JG, Levi R. Nitric oxide in the regulation of blood flow and arterial pressure. Annu Rev Physiol 57: 771-790 (1995).
30. Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A 88(11): 4651-4655 (1991).
31. Jeremy JY, Rowe D, Emsley AM, Newby AC. Nitric oxide and the proliferation of vascular smooth muscle cells. Cardiovasc Res 43(3): 580-594 (1999).
32. Loscalzo J. Nitric oxide insufficiency, platelet activation, and arterial thrombosis. Circ Res 88(8): 756-762 (2001).
33. Gottesman RF, Hillis AE. Predictors and assessment of cognitive dysfunction resulting from ischaemic stroke. Lancet Neurol 9(9): 895-905 (2010).
34. Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 341: c3666 (2010).
35. de la Torre JC, Aliev G. Inhibition of vascular nitric oxide after rat chronic brain hypoperfusion: spatial memory and immunocytochemical changes. J Cereb Blood Flow Metab 25(6): 663-672 (2005).
36. Austin SA, Santhanam AV, Katusic ZS. Endothelial nitric oxide modulates expression and processing of amyloid precursor protein. Circ Res 107(12): 1498-1502 (2010).
37. Corzo L, Zas R, Rodriguez S, Fernandez-Novoa L, Cacabelos R. Decreased levels of serum nitric oxide in different forms of dementia. Neurosci Lett 420(3): 263-267 (2007).
38. Ntais C, Polycarpou A. Association of the endothelial nitric oxide synthase (NOS3) Glu298Asp gene polymorphism with the risk of Alzheimer's disease-a meta-analysis. J Neurol 252(10): 1276-1278 (2005).
39. Guix FX, Uribesalgo I, Coma M, Munoz FJ. The physiology and pathophysiology of nitric oxide in the brain. Prog Neurobiol 76(2): 126-152 (2005).
40. Vincent SR. Nitric oxide neurons and neurotransmission. Prog Neurobiol 90(2): 246-255(2010).
41. Contestabile A, Ciani E. Role of nitric oxide in the regulation of neuronal proliferation, survival and differentiation. Neurochem Int 45(6): 903-914 (2004).
42. Hetrick EM, Schoenfisch MH. Analytical chemistry of nitric oxide. Annu Rev Anal Chem (Palo Alto Calif) 2: 409-433 (2009).
43. Rejdak K, Petzold A, Sharpe MA, Kay AD, Kerr M, Keir G, et al. Cerebrospinal fluid nitrite/nitrate correlated with oxyhemoglobin and outcome in patients with subarachnoid hemorrhage. J Neurol Sci 219(1-2): 71-76 (2004).
44. Wagner DA, Schultz DS, Deen WM, Young VR, Tannenbaum SR. Metabolic fate of an oral dose of 15N-labeled nitrate in humans: effect of diet supplementation with ascorbic acid. Cancer Res 43(4): 1921-1925 (1983).
45. Ellis G, Adatia I, Yazdanpanah M, Makela SK. Nitrite and nitrate analyses: a clinical biochemistry perspective. Clin Biochem 31(4): 195-220 (1998).
46. Tsikas D. Assessment of nitric oxide biosynthesis and peroxynitrite formation within the central nervous system by measuring Lcitrulline in the cerebrospinal fluid? J Chromatogr B Analyt Technol Biomed Life Sci 813(1-2): 359-361 (2004).
47. Schwedhelm E. Quantification of ADMA: analytical approaches. Vasc Med 10(1): S89-S95 (2005).
48. Wadham C, Mangoni AA. Dimethylarginine dimethylaminohydrolase regulation: a novel therapeutic target in cardiovascular disease. Expert Opin Drug Metab Toxicol 5(3): 303-319 (2009).
49. Bedford MT, Richard S. Arginine methylation an emerging regulator of protein function. Mol Cell 18(3): 263-272 (2005).
50. Duerre JA, Miller CH, Reams GG. Metabolism of S-adenosyl-Lhomocysteine in vivo by the rat. J Biol Chem 244(1): 107-111 (1969).
51. Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, et al. Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306(5694): 279-283 (2004).
52. Cuthbert GL, Daujat S, Snowden AW, Erdjument-Bromage H, Hagiwara T, Yamada M, et al. Histone deimination antagonizes arginine methylation. Cell 118(5): 545-553 (2004).
53. Boger 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 87(2): 99-105 (2000).
54. Cardounel AJ, Cui H, Samouilov A, Johnson W, Kearns P, Tsai AL, et al. Evidence for the pathophysiological role of endogenous methylarginines in regulation of endothelial NO production and vascular function. J Biol Chem 282(2): 879-887 (2007).
55. Ogawa T, Kimoto M, Sasaoka K. Purification and properties of a new enzyme, NG, NG-dimethylarginine dimethylaminohydrolase, from rat kidney. J Biol Chem 264(17): 10205-10209 (1989).
56. Murray-Rust J, Leiper J, McAlister M, Phelan J, Tilley S, Santa Maria J, et al. Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase. Nat Struct Biol 8(8): 679-683 (2001).
57. Leiper J, Murray-Rust J, McDonald N, Vallance P. S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase. Proc Natl Acad Sci U S A 99(21): 13527-13532 (2002).
58. Closs EI, Basha FZ, Habermeier A, Forstermann U. Interference of L-arginine analogues with L-arginine transport mediated by the y+ carrier hCAT-2B. Nitric Oxide 1(1): 65-73 (1997).
59. Stoll J, Wadhwani KC, Smith QR. Identification of the cationic amino acid transporter (System y+) of the rat blood-brain barrier. J Neurochem 60(5): 1956-1959 (1993).
60. Mahar Doan KM, Lakhman SS, Boje KM. Blood-brain barrier transport studies of organic guanidino cations using an in situ brain perfusion technique. Brain Res 876(1-2): 141-147 (2000).
61. Suda O, Tsutsui M, Morishita T, et al. Asymmetric dimethylarginine produces vascular lesions in endothelial nitric oxide synthasedeficient mice: involvement of renin-angiotensin system and oxidative stress. Arterioscler Thromb Vasc Biol 24(9): 1682-1688 (2004).
62. Selley ML. Increased concentrations of homocysteine and asymmetric dimethylarginine and decreased concentrations of nitric oxide in the plasma of patients with Alzheimer's disease. Neurobiol Aging 24(7): 903-907 (2003).
63. Abe T, Tohgi H, Murata T, Isobe C, Sato C. Reduction in asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in the cerebrospinal fluid during aging and in patients with Alzheimer's disease. Neurosci Lett 312(3): 177-179 (2001).
64. Mulder C, Wahlund LO, Blomberg M, de Jong S, van Kamp GJ, Scheltens P, et al. Alzheimer's disease is not associated with altered concentrations of the nitric oxide synthase inhibitor asymmetric dimethylarginine in cerebrospinal fluid. J Neural Transm 109(9): 1203-1208 (2002).
65. Arlt S, Schulze F, Eichenlaub M, et al. Asymmetrical dimethylarginine is increased in plasma and decreased in cerebrospinal fluid of patients with Alzheimer's disease. Dement Geriatr Cogn Disord 26(1): 58-64 (2008).
66. Smith MA, Vasak M, Knipp M, Castellani RJ, Perry G. Dimethylargininase, a nitric oxide regulatory protein, in Alzheimer disease. Free Radic Biol Med 25(8): 898-902 (1998).
67. Moncada S, Bolanos JP. Nitric oxide, cell bioenergetics and neurodegeneration. J Neurochem 97(6): 1676-1689 (2006).
68. McEvoy M, Smith W, D'Este C, Duke J, Peel R, Schofield P, et al. Cohort profile: The Hunter Community Study. Int J Epidemiol 39(6): 1452-1463 (2010).
69. Maas R. Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA). Vasc Med 10(1): S49-S57 (2005).
70. Leiper J, Nandi M. The therapeutic potential of targeting endogenous inhibitors of nitric oxide synthesis. Nat Rev Drug Discov 10(4): 277-291 (2011).
71. Palm F, Onozato ML, Luo Z, Wilcox CS. Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems. Am J Physiol Heart Circ Physiol 293(6): H3227-H3245 (2007).
72. Sano M, Bell KL, Galasko D, Galvin JE, Thomas RG, van Dyck CH, et al. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology 77(6): 556-563 (2011).
73. Carlsson CM, Gleason CE, Hess TM, Moreland KA, Blazel HM, Koscik RL, et al. Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer's disease. J Alzheimers Dis 13(2):187-197 (2008).
74. Feldman HH, Doody RS, Kivipelto M, Sparks DL, Waters DD, Jones RW, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology 74(12): 956-964 (2010).
75. Sparks DL, Sabbagh MN, Connor DJ, Lopez J, Launer LJ, Browne P, et al. Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results. Arch Neurol 62(5): 753-757 (2005).
76. Bentham P, Gray R, Sellwood E, Hills R, Crome P, Raftery J. Aspirin in Alzheimer's disease (AD2000): a randomised open-label trial. Lancet Neurol 7(1): 41-49 (2008).
77. Tzourio C, Anderson C, Chapman N, Woodward M, Neal B, MacMahon S, et al. Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med 163(9): 1069-1075 (2003).
78. Anderson C, Teo K, Gao P, Arima H, Dans A, Unger T, et al. Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies. Lancet Neurol 10(1): 43-53 (2011).
79. Harrington C, Sawchak S, Chiang C, Davies J, Donovan C, Saunders AM, et al. Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies. Curr Alzheimer Res 8(5): 592-606 (2011).
80. Risner ME, Saunders AM, Altman JF, Ormandy GC, Craft S, Foley IM, et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenomics J 6(4): 246-254 (2006).
81. Sato T, Hanyu H, Hirao K, Kanetaka H, Sakurai H, Iwamoto T. Efficacy of PPAR-gamma agonist pioglitazone in mild Alzheimer disease. Neurobiol Aging 32(9): 1626-1633 (2011).
82. Wharton W, Baker LD, Gleason CE, Dowling M, Barnet JH, Johnson S, et al. Short-term hormone therapy with transdermal estradiol improves cognition for postmenopausal women with Alzheimer's disease: results of a randomized controlled trial. J Alzheimers Dis 26(3): 495-505 (2011).
83. Asthana S, Baker LD, Craft S, Stanczyk FZ, Veith RC, Raskind MA, et al. High-dose estradiol improves cognition for women with AD: results of a randomized study. Neurology 57(4): 605-612 (2001).
84. Valen-Sendstad A, Engedal K, Stray-Pedersen B et al. Effects of hormone therapy on depressive symptoms and cognitive functions in women with Alzheimer disease: a 12 month randomized, doubleblind, placebo-controlled study of low-dose estradiol and norethisterone. Am J Geriatr Psychiatry 18(1): 11-20 (2010).
85. Almeida OP, Lautenschlager NT, Vasikaran S, Leedman P, Gelavis A, Flicker L. A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: effect on mood, cognition and quality of life. Neurobiol Aging 27(1): 141-149 (2006).
86. Espeland MA, Brunner RL, Hogan PE, Rapp SR, Coker LH, Legault C, et al. Long-term effects of conjugated equine estrogen therapies on domain-specific cognitive function: results from the Women's Health Initiative study of cognitive aging extension. J Am Geriatr Soc 58(7): 1263-1271 (2010).
87. Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA 291(24): 2959-2968 (2004).
88. Shumaker SA, Legault C, Rapp SR et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 289(20): 2651-2662 (2003).
89. Resnick SM, Espeland MA, An Y, Maki PM, Coker LH, Jackson R, et al. Effects of conjugated equine estrogens on cognition and affect in postmenopausal women with prior hysterectomy. J Clin Endocrinol Metab 94(11): 4152-4161 (2009).
90. Rapp SR, Espeland MA, Shumaker SA, Henderson VW, Brunner RL, Manson JE, et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 289(20): 2663-2672 (2003).