Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1023-1030
Published online before print April 22, 2004, doi: 10.1161/01.ATV.0000128897.54893.26
Published online before print April 22, 2004, doi: 10.1161/01.ATV.0000128897.54893.26
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2004 American Heart Association, Inc.
Brief Reviews |
Cardiovascular Biology of the Asymmetric Dimethylarginine:Dimethylarginine Dimethylaminohydrolase Pathway
From the BHF Laboratories, Division of Medicine, University College London, London, UK.
Correspondence to Patrick Vallance, University College London, Rayne Institute, 5 University St, London WC1 6JJ, UK. E-mail patrick.vallance{at}ucl.ac.uk
An increasing number of reports indicate that endogenously produced inhibitors of nitric oxide synthase, particularly asymmetric dimethylarginine (ADMA), regulate nitric oxide generation in disease states. This article describes the biology of ADMA and the implications for cardiovascular physiology and pathophysiology.
An increasing number of reports indicate that endogenously produced inhibitors of nitric oxide synthase, particularly asymmetric dimethylarginine (ADMA), regulate nitric oxide generation in disease states. This article describes the biology of ADMA and the implications for cardiovascular physiology and pathophysiology.
Key Words: asymmetric dimethylarginine • dimethylarginine dimethylaminohydrolase • nitric oxide synthase • endothelial dysfunction
This article has been cited by other articles:
 |
|
 |
|
  J. Li, A. Wilson, X. Gao, R. Kuruba, Y. Liu, S. Poloyac, B. Pitt, W. Xie, and S. Li Coordinated Regulation of Dimethylarginine Dimethylaminohydrolase-1 and Cationic Amino Acid Transporter-1 by Farnesoid X Receptor in Mouse Liver and Kidney and Its Implication in the Control of Blood Levels of Asymmetric Dimethylarginine J. Pharmacol. Exp. Ther., October 1, 2009; 331(1): 234 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Potenza, S. Gagliardi, L. De Benedictis, A. Zigrino, E. Tiravanti, G. Colantuono, A. Federici, L. Lorusso, V. Benagiano, M. J. Quon, et al. Treatment of spontaneously hypertensive rats with rosiglitazone ameliorates cardiovascular pathophysiology via antioxidant mechanisms in the vasculature Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E685 - E694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Musicki, A. E. Ross, H. C. Champion, A. L. Burnett, and T. J. Bivalacqua Posttranslational Modification of Constitutive Nitric Oxide Synthase in the Penis J Androl, July 1, 2009; 30(4): 352 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-L. Balligand, O. Feron, and C. Dessy eNOS Activation by Physical Forces: From Short-Term Regulation of Contraction to Chronic Remodeling of Cardiovascular Tissues Physiol Rev, April 1, 2009; 89(2): 481 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wang, S. Strandgaard, J. Iversen, and C. S. Wilcox Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R195 - R200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Wojciak-Stothard, B. Torondel, L. Zhao, T. Renne, and J. M. Leiper Modulation of Rac1 Activity by ADMA/DDAH Regulates Pulmonary Endothelial Barrier Function Mol. Biol. Cell, January 1, 2009; 20(1): 33 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Siekmeier, T. Grammer, and W. Marz Roles of Oxidants, Nitric Oxide, and Asymmetric Dimethylarginine in Endothelial Function Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2008; 13(4): 279 - 297. [Abstract] [PDF]
|
|
|
|
 |
|
 J. A. Chirinos, R. David, J. A. Bralley, H. Zea-Diaz, E. Munoz-Atahualpa, F. Corrales-Medina, C. Cuba-Bustinza, J. Chirinos-Pacheco, and J. Medina-Lezama Endogenous Nitric Oxide Synthase Inhibitors, Arterial Hemodynamics, and Subclinical Vascular Disease: The PREVENCION Study Hypertension, December 1, 2008; 52(6): 1051 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Richir, R. H. Bouwman, T. Teerlink, M. P.C. Siroen, T. P.G.M. de Vries, and P. A.M. van Leeuwen The Prominent Role of the Liver in the Elimination of Asymmetric Dimethylarginine (ADMA) and the Consequences of Impaired Hepatic Function JPEN J Parenter Enteral Nutr, November 1, 2008; 32(6): 613 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. H. Wilson Tang, W. Tong, K. Shrestha, Z. Wang, B. S. Levison, B. Delfraino, B. Hu, R. W. Troughton, A. L. Klein, and S. L. Hazen Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure Eur. Heart J., October 2, 2008; 29(20): 2506 - 2513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Stoessel, A. Paliege, F. Theilig, F. Addabbo, B. Ratliff, J. Waschke, D. Patschan, M. S. Goligorsky, and S. Bachmann Indolent course of tubulointerstitial disease in a mouse model of subpressor, low-dose nitric oxide synthase inhibition Am J Physiol Renal Physiol, September 1, 2008; 295(3): F717 - F725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dayal, R. N. Rodionov, E. Arning, T. Bottiglieri, M. Kimoto, D. J. Murry, J. P. Cooke, F. M. Faraci, and S. R. Lentz Tissue-specific downregulation of dimethylarginine dimethylaminohydrolase in hyperhomocysteinemia Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H816 - H825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Surdacki, E. Marewicz, E. Wieteska, G. Szastak, T. Rakowski, E. Wieczorek-Surdacka, D. Dudek, J. Pryjma, and J. S. Dubiel Association between endothelial progenitor cell depletion in blood and mild-to-moderate renal insufficiency in stable angina Nephrol. Dial. Transplant., July 1, 2008; 23(7): 2265 - 2273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wipff, J. Avouac, D. Borderie, D. Zerkak, H. Lemarechal, A. Kahan, C. Boileau, and Y. Allanore Disturbed angiogenesis in systemic sclerosis: high levels of soluble endoglin Rheumatology, July 1, 2008; 47(7): 972 - 975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Scalera, J. Martens-Lobenhoffer, A. Bukowska, U. Lendeckel, M. Tager, and S. M. Bode-Boger Effect of Telmisartan on Nitric Oxide-Asymmetrical Dimethylarginine System: Role of Angiotensin II Type 1 Receptor and Peroxisome Proliferator Activated Receptor {gamma} Signaling During Endothelial Aging Hypertension, March 1, 2008; 51(3): 696 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. Yilmaz, A. Sonmez, M. Saglam, A. R. Qureshi, J. J. Carrero, K. Caglar, T. Eyileten, E. Cakir, Y. Oguz, A. Vural, et al. ADMA Levels Correlate with Proteinuria, Secondary Amyloidosis, and Endothelial Dysfunction J. Am. Soc. Nephrol., February 1, 2008; 19(2): 388 - 395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jacobi, R. Maas, N. Cordasic, K. Koch, R. E. Schmieder, R. H. Boger, and K. F. Hilgers Role of asymmetric dimethylarginine for angiotensin II-induced target organ damage in mice Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H1058 - H1066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Dayoub, R. N. Rodionov, C. Lynch, J. P. Cooke, E. Arning, T. Bottiglieri, S. R. Lentz, and F. M. Faraci Overexpression of Dimethylarginine Dimethylaminohydrolase Inhibits Asymmetric Dimethylarginine-Induced Endothelial Dysfunction in the Cerebral Circulation Stroke, January 1, 2008; 39(1): 180 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Palm, M. L. Onozato, Z. Luo, and C. S. Wilcox Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3227 - H3245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Nicholls, Z. Wang, R. Koeth, B. Levison, B. DelFraino, V. Dzavik, O. W. Griffith, D. Hathaway, J. A. Panza, S. E. Nissen, et al. Metabolic Profiling of Arginine and Nitric Oxide Pathways Predicts Hemodynamic Abnormalities and Mortality in Patients With Cardiogenic Shock After Acute Myocardial Infarction Circulation, November 13, 2007; 116(20): 2315 - 2324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Pope, L. Druhan, J. E. Guzman, S. P. Forbes, V. Murugesan, D. Lu, Y. Xia, L. G. Chicoine, N. L. Parinandi, and A. J. Cardounel Role of DDAH-1 in lipid peroxidation product-mediated inhibition of endothelial NO generation Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1679 - C1686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Juonala, J. S.A. Viikari, G. Alfthan, J. Marniemi, M. Kahonen, L. Taittonen, T. Laitinen, and O. T. Raitakari Brachial Artery Flow-Mediated Dilation and Asymmetrical Dimethylarginine in the Cardiovascular Risk in Young Finns Study Circulation, September 18, 2007; 116(12): 1367 - 1373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Duckelmann, F. Mittermayer, D. G. Haider, J. Altenberger, J. Eichinger, and M. Wolzt Asymmetric Dimethylarginine Enhances Cardiovascular Risk Prediction in Patients With Chronic Heart Failure Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 2037 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Schiffrin, M. L. Lipman, and J. F.E. Mann Chronic Kidney Disease: Effects on the Cardiovascular System Circulation, July 3, 2007; 116(1): 85 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Maas, F. Schulze, J. Baumert, H. Lowel, K. Hamraz, E. Schwedhelm, W. Koenig, and R. H. Boger Asymmetric Dimethylarginine, Smoking, and Risk of Coronary Heart Disease in Apparently Healthy Men: Prospective Analysis from the Population-Based Monitoring of Trends and Determinants in Cardiovascular Disease/Kooperative Gesundheitsforschung in der Region Augsburg Study and Experimental Data Clin. Chem., April 1, 2007; 53(4): 693 - 701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Wojciak-Stothard, B. Torondel, L. Y. F. Tsang, I. Fleming, B. Fisslthaler, J. M. Leiper, and P. Vallance The ADMA/DDAH pathway is a critical regulator of endothelial cell motility J. Cell Sci., March 15, 2007; 120(6): 929 - 942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Deanfield, J. P. Halcox, and T. J. Rabelink Endothelial Function and Dysfunction: Testing and Clinical Relevance Circulation, March 13, 2007; 115(10): 1285 - 1295. [Full Text] [PDF]
|
|
|
|
|
|
S. Tatematsu, S. Wakino, T. Kanda, K. Homma, K. Yoshioka, K. Hasegawa, N. Sugano, M. Kimoto, T. Saruta, and K. Hayashi Role of Nitric Oxide-Producing and -Degrading Pathways in Coronary Endothelial Dysfunction in Chronic Kidney Disease J. Am. Soc. Nephrol., March 1, 2007; 18(3): 741 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Toth, A. Racz, P. M. Kaminski, M. S. Wolin, Z. Bagi, and A. Koller Asymmetrical Dimethylarginine Inhibits Shear Stress-Induced Nitric Oxide Release and Dilation and Elicits Superoxide-Mediated Increase in Arteriolar Tone Hypertension, March 1, 2007; 49(3): 563 - 568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M.C. Brunini, A. C. Mendes-Ribeiro, J. C. Ellory, and G. E. Mann Platelet nitric oxide synthesis in uremia and malnutrition: A role for L-arginine supplementation in vascular protection? Cardiovasc Res, January 15, 2007; 73(2): 359 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Cardounel, H. Cui, A. Samouilov, W. Johnson, P. Kearns, A.-L. Tsai, V. Berka, and J. L. Zweier Evidence for the Pathophysiological Role of Endogenous Methylarginines in Regulation of Endothelial NO Production and Vascular Function J. Biol. Chem., January 12, 2007; 282(2): 879 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bulau, D. Zakrzewicz, K. Kitowska, J. Leiper, A. Gunther, F. Grimminger, and O. Eickelberg Analysis of methylarginine metabolism in the cardiovascular system identifies the lung as a major source of ADMA Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L18 - L24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Monsalve, P. J. Oviedo, M. A. Garcia-Perez, J. J. Tarin, A. Cano, and C. Hermenegildo Estradiol counteracts oxidized LDL-induced asymmetric dimethylarginine production by cultured human endothelial cells Cardiovasc Res, January 1, 2007; 73(1): 66 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hu, M. Chouinard, A. L. Cox, P. Sipes, M. Marcelo, J. Ficorilli, S. Li, H. Gao, T. P. Ryan, M. D. Michael, et al. Farnesoid X Receptor Agonist Reduces Serum Asymmetric Dimethylarginine Levels through Hepatic Dimethylarginine Dimethylaminohydrolase-1 Gene Regulation J. Biol. Chem., December 29, 2006; 281(52): 39831 - 39838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. O. Yildirim, P. Bulau, D. Zakrzewicz, K. E. Kitowska, N. Weissmann, F. Grimminger, R. E. Morty, and O. Eickelberg Increased Protein Arginine Methylation in Chronic Hypoxia: Role of Protein Arginine Methyltransferases Am. J. Respir. Cell Mol. Biol., October 1, 2006; 35(4): 436 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yang, R. Ji, Y. Cheng, J.-Z. Sun, L. K. Jennings, and C. Zhang L-Arginine Chlorination Results in the Formation of a Nonselective Nitric-Oxide Synthase Inhibitor J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1044 - 1049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Amann, C. Wanner, and E. Ritz Cross-Talk between the Kidney and the Cardiovascular System J. Am. Soc. Nephrol., August 1, 2006; 17(8): 2112 - 2119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Dooley, B. Gao, N. Bradley, D. J. Abraham, C. M. Black, M. Jacobs, and K. R. Bruckdorfer Abnormal nitric oxide metabolism in systemic sclerosis: increased levels of nitrated proteins and asymmetric dimethylarginine Rheumatology, June 1, 2006; 45(6): 676 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Yamamoto and Y. Aso Synergistic Association of Metabolic Syndrome and Overt Nephropathy With Elevated Asymmetric Dimethylarginine in Serum and Impaired Cutaneous Microvasodilation in Patients With Type 2 Diabetes Diabetes Care, April 1, 2006; 29(4): 928 - 930. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yang and X.-F. Ming Recent advances in understanding endothelial dysfunction in atherosclerosis. Clin. Med. Res., March 1, 2006; 4(1): 53 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Rabelink and T. F. Luscher Endothelial Nitric Oxide Synthase: Host Defense Enzyme of the Endothelium? Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): 267 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Louden, D. Brott, A. Katein, T. Kelly, S. Gould, H. Jones, G. Betton, J.-P. Valetin, and R. J. Richardson Biomarkers and Mechanisms of Drug-Induced Vascular Injury in Non-Rodents Toxicol Pathol, January 1, 2006; 34(1): 19 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. T. Chan, P. J. Harvey, R. Boger, A. Pierratos, and J. S. Floras Letter to the Editor: Dissociation Between the Short-Term Effects of Nocturnal Hemodialysis on Endothelium Dependent Vasodilation and Plasma ADMA Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2685 - 2686. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kanaganayagam and M. S. Marber ADMAring Endothelial Progenitor Cells: Accident, Association, or Antecedent J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1702 - 1704. [Full Text] [PDF]
|
|
|
|
 |
|
 L C Jones and A D Hingorani Genetic regulation of endothelial function Heart, October 1, 2005; 91(10): 1275 - 1277. [Full Text] [PDF]
|
|
|
|
|
|
T. K. Krempl, R. Maas, K. Sydow, T. Meinertz, R. H. Boger, and J. Kahler Elevation of asymmetric dimethylarginine in patients with unstable angina and recurrent cardiovascular events Eur. Heart J., September 2, 2005; 26(18): 1846 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Ravani, G. Tripepi, F. Malberti, S. Testa, F. Mallamaci, and C. Zoccali Asymmetrical Dimethylarginine Predicts Progression to Dialysis and Death in Patients with Chronic Kidney Disease: A Competing Risks Modeling Approach J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2449 - 2455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Vallance and J. Leiper Asymmetric Dimethylarginine and Kidney Disease--Marker or Mediator? J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2254 - 2256. [Full Text] [PDF]
|
|
|
|
 |
|
 R. H Boger, J. P Cooke, and P. Vallance ADMA: an emerging cardiovascular risk factor Vascular Medicine, July 1, 2005; 10(1_suppl): S1 - S2. [PDF]
|
|
|
|
|
|
R. H Boger Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials Vascular Medicine, July 1, 2005; 10(1_suppl): S19 - S25. [Abstract] [PDF]
|
|
|
|
|
|
R. Maas Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA) Vascular Medicine, July 1, 2005; 10(1_suppl): S49 - S57. [Abstract] [PDF]
|
|
|
|
|
|
M. Herrera and J. L. Garvin Recent Advances in the Regulation of Nitric Oxide in the Kidney Hypertension, June 1, 2005; 45(6): 1062 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H Boger, J. P Cooke, and P. Vallance ADMA: an emerging cardiovascular risk factor Vascular Medicine, May 1, 2005; 10(2_suppl): S1 - S2. [PDF]
|
|
|
|
|
|
R. H Boger Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials Vascular Medicine, May 1, 2005; 10(2_suppl): S19 - S25. [Abstract] [PDF]
|
|
|
|
|
|
R. Maas Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA) Vascular Medicine, May 1, 2005; 10(2_suppl): S49 - S57. [Abstract] [PDF]
|
|
|
|
|
|
F. Scalera, J. T. Kielstein, J. Martens-Lobenhoffer, S. C. Postel, M. Tager, and S. M. Bode-Boger Erythropoietin Increases Asymmetric Dimethylarginine in Endothelial Cells: Role of Dimethylarginine Dimethylaminohydrolase J. Am. Soc. Nephrol., April 1, 2005; 16(4): 892 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Krzyzanowska, F. Mittermayer, H.-P. Kopp, M. Wolzt, and G. Schernthaner Weight Loss Reduces Circulating Asymmetrical Dimethylarginine Concentrations in Morbidly Obese Women J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6277 - 6281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Henderson, J. R. Turk, J. W. E. Rush, and M. H. Laughlin Endothelial function in coronary arterioles from pigs with early-stage coronary disease induced by high-fat, high-cholesterol diet: effect of exercise J Appl Physiol, September 1, 2004; 97(3): 1159 - 1168. [Abstract] [Full Text] [PDF]
|
|