(Circulation. 1999;99:3092-3095.)
© 1999 American Heart Association, Inc.
Brief Rapid Communications |
Novel Mechanism for Endothelial Dysfunction
Dysregulation of Dimethylarginine Dimethylaminohydrolase
From the Division of Cardiovascular Medicine, Stanford University School of Medicine (A.I., P.S.T., S.A., J.P.C.), Stanford, Calif; the Department of Nutritional Science, Okayama Prefectural University (M.K.), Kuboki, Japan; and Research Institute for Food Science, Kyoto University (T.O.), Uji, Japan.
Correspondence to John P. Cooke, MD, PhD, Associate Professor, Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305-5246. E-mail John.Cooke{at}stanford.edu
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Abstract |
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Background—Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS). Plasma levels of ADMA are elevated in individuals with hypercholesterolemia or atherosclerosis. We postulated that reduced degradation of ADMA may play a role in the accumulation of ADMA in these individuals. Accordingly, we studied the effects of oxidized LDL (oxLDL) or tumor necrosis factor-
(TNF-) on the accumulation of
ADMA by transformed human umbilical vein endothelial
cells (ECV304) and on the enzyme dimethylarginine
dimethylaminohydrolase (DDAH), which degrades ADMA.
Methods and Results—ECV304 were incubated with or without native
LDL (100 µg/mL), oxLDL (100 µg/mL), or TNF- (250 U/mL) for 48
hours. The concentration of ADMA in the conditioned medium was
determined by high-performance liquid
chromatography. Western blotting was performed to
evaluate DDAH expression. We assayed DDAH activity by determining
L-citrulline formation from ADMA. The addition of oxLDL or
TNF- to ECV304 significantly increased the level of ADMA in the
conditioned medium. The effect of oxLDL or TNF- was not due to a
change in DDAH expression but rather to the reduction of DDAH activity.
To determine whether dysregulation of DDAH also occurred in vivo, New
Zealand White rabbits were fed normal chow or a
high-cholesterol diet.
Hypercholesterolemia significantly reduced
aortic, renal, and hepatic DDAH activity.
Conclusions—These results suggest that the endothelial vasodilator dysfunction observed in hypercholesterolemia may be due to reduced degradation of ADMA, the endogenous inhibitor of NOS.
Key Words: lipoproteins • endothelium • amino acids • asymmetric dimethylarginine • nitric oxide
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Introduction |
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Endothelium-derived nitric oxide (NO) is a potent vasodilator that plays a critical role in regulating vascular resistance and flow.1 In addition, NO inhibits key processes in atherogenesis, such as monocyte adhesion, platelet aggregation, and vascular smooth muscle proliferation.2 In metabolic disorders associated with atherosclerosis (eg, hypercholesterolemia, hypertension, and diabetes mellitus), a reduced endothelium-mediated, NO-dependent vasodilation is observed, which may contribute to the initiation and progression of atherosclerosis associated with these disorders.2 Although the mechanisms of endothelial vasodilator dysfunction are likely multifactorial, one contributing abnormality appears to be increased levels of asymmetric dimethylarginine (ADMA).
ADMA is an endogenous competitive inhibitor of NO synthase.3 It is thought to be derived from proteins that have been posttranslationally methylated and subsequently hydrolyzed to release ADMA.4 A number of cells elaborate ADMA, including human endothelial cells.5 ADMA may be excreted in the urine or metabolized by the enzyme dimethylarginine dimethyl-aminohydrolase (DDAH).6 This enzyme hydrolyzes ADMA to L-citrulline and dimethylamine. We hypothesized that lipid-induced dysregulation of DDAH may play an important role in the elevation of ADMA and the derangement of the NO synthase pathway in hypercholesterolemia.
Accordingly, we studied the effects of lipoprotein on the endothelial elaboration of ADMA and on the expression and activity of DDAH in cell culture and in vivo.
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Methods |
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Cell Culture
Spontaneously transformed human umbilical vein endothelial cells (ECV304; ATCC) were cultured in medium M199 (Irvine Scientific) containing 10% FCS, 100 U/mL penicillin, and 100 µg/mL streptomycin (Gibco BRL). This cell line retains many of the characteristics of primary endothelial cells, including the synthesis of NO.7
At 80% confluence, cells were washed and replaced with serum-free
medium. After 2 hours, cells were incubated in the presence or absence
(control) of native LDL (100 µg/mL), oxidized LDL (oxLDL; 30 or 100
µg/mL), or tumor necrosis factor- (TNF-; 250 U/mL) for 0, 24,
or 48 hours. To assess cell viability, lactate dehydrogenase activity
in the conditioned medium was determined by a spectrophotometric assay
(Sigma Diagnostics).
Lipoprotein Preparation
LDL was isolated by density-gradient
ultracentrifugation of normal human plasma collected in
EDTA (1 mg/mL) and quantified by Lowry assay.8 OxLDL was
prepared by incubation of LDL (100 µg/mL) with
CuSO4 (10 µg/mL) at 37°C for 24 hours. The
extent of oxidization was monitored by measurement of thiobarbituric
acid–reactive substances at 550 Å.8
Measurement of ADMA
Concentrations of L-arginine and ADMA in the
conditioned medium were measured by high-performance liquid
chromatography and precolumn derivatization with
o-phthaldialdehyde, as previously
described.9
Western Blotting
Cells were resuspended in 500 µL of 0.1 mol/L sodium phosphate
buffer (pH 7.0) and subsequently lysed by rapid freezing and thawing.
Cell lysates were centrifuged at 15 000 rpm for 40 minutes,
and supernatants were used for Western blotting and enzyme activity
assay. Protein concentrations were measured by Lowry assay.
Membranes with transferred proteins were incubated with a mouse monoclonal antibody raised against purified rat DDAH6 (1:1000) in Tris-buffered saline containing 4% nonfat milk and probed with a peroxidase-conjugated anti-mouse antibody (1:1000), with detection by ECL Western blotting reagents (Amersham).
Enzyme Assay
We assayed DDAH activity by determining L-citrulline
formation in cell lysates, as previously described.10 As
negative controls, cell lysates were boiled for 10 minutes to
inactivate the enzyme, and L-citrulline
formation was determined. Background values obtained were subtracted
from the experimental data to provide genuine DDAH activity.
Data Analysis
Data are expressed as mean±SEM. Comparisons of multiple means
were made by ANOVA followed by a Fisher's protected least significant
difference test. Comparisons between treatment groups in the rabbit
study were made by Student's unpaired t test. A value of
P<0.05 was accepted as statistically significant.
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Results |
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ADMA Elaboration by Endothelial Cells
The concentration of ADMA in the conditioned medium of control cells gradually increased with time to a level of 0.6±0.2 µmol/L at 48 hours (Figure 1
).
Incubation with native LDL (100 µg/mL) or a low dose of oxLDL (30
µg/mL) tended to increase the accumulation of ADMA (native LDL,
1.1±0.4 µmol/L; oxLDL, 1.2±0.3 µmol/L at 48 hours).
Incubation with a high dose of oxLDL (100 µg/mL) or TNF- (250
U/mL) for 48 hours significantly augmented ADMA accumulation (oxLDL,
3.9±1.3 µmol/L, P<0.05; TNF-, 4.9±1.5
µmol/L, P=0.01) (Figure 1).
L-Arginine concentrations in the medium did not
change among 5 groups throughout the experimental period. Lactate
dehydrogenase activity in the conditioned medium from
endothelial cells incubated with native LDL, oxLDL, or
TNF- was not significantly higher than in medium from control cells
(data not shown).
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DDAH Expression and Activity
Incubation with oxLDL (100 µg/mL) or TNF- caused no changes
in the expression of protein levels of DDAH throughout the experimental
period, as assessed by Western blot analysis (Figure 2A). DDAH activity was significantly
decreased by 48-hour incubation with oxLDL (100 µg/mL) (63±8%;
P=0.01) or TNF- (63±8%; P=0.01), whereas
control cells exhibited no significant change in DDAH activity
(95±6%) (Figure 2B).
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To determine whether this cytokine or lipid-induced
dysregulation of DDAH occurred in vivo, New Zealand White rabbits were
fed a normal chow (n=4) or 1% cholesterol diet (n=5).
Bode-Boger et al11 previously showed that in this animal
model, hypercholesterolemia increased plasma
ADMA from 1.2 to 2.0 µmol/L. At 12 weeks, animals were killed,
and the aortae, livers, and kidneys were removed for analysis
of DDAH expression and activity. There were no differences between
control and hypercholesterolemic animals in DDAH
expression of the aorta, kidney, or liver (data not shown). However,
DDAH activity in each of these tissues was significantly decreased in
hypercholesterolemic animals
(Table).
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Discussion |
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The salient findings of this study are as follows: (1) OxLDL or TNF-
increases ADMA elaboration by endothelial
cells. (2) This effect is associated with decreased DDAH activity,
without a change in protein expression. (3) A similar dysregulation of
DDAH activity is observed in vascular and extravascular tissues in
rabbits fed a high-cholesterol diet. The data suggest that
reduced activity of DDAH may be responsible for the elevated plasma
ADMA and endothelial vasodilator dysfunction in
hypercholesterolemia.
This study provides insight into a novel mechanism by which
hyperlipidemia may disturb the NO synthase pathway in
endothelial cells. Increased levels of ADMA, the
endogenous NO synthase inhibitor, are observed
in hypercholesterolemic animals and humans and may
account for the endothelial vasodilator dysfunction
observed in this condition.9 11 ADMA plasma levels, which
are 1.0±0.1 µmol/L in healthy humans, are elevated 2-fold in
hypercholesterolemic individuals9 and
3-fold in elderly patients with peripheral
arterial occlusive disease and generalized
atherosclerosis.12 Increased ADMA levels
are associated with reduced NO elaboration in
hypercholesterolemic subjects and in atherosclerotic
patients, as judged by reduced nitrate excretion and impaired
endothelium-dependent, NO-mediated forearm
vasodilation.9 12 Previous studies have shown that
exogenous ADMA concentrations between 1 and 10 µmol/L affect
endothelium-dependent, NO-mediated vasodilation in rat
mesenteric vessels13 and rat cerebral
vessels14 and also regulate NO production by
cultured macrophages.5 In the present study,
the concentration of ADMA in the conditioned medium was increased 6- or
8-fold by incubation with oxLDL (100 µg/mL) or TNF-, respectively,
compared with control. These increases of ADMA may have
pathophysiological significance, because they are
in a range to inhibit the activity of NO synthase.
In humans, ADMA may be excreted by the kidney or metabolized by
DDAH.6 We found that protein levels of DDAH were
unaffected by oxLDL or TNF-. By contrast, DDAH activity of
endothelial cells was decreased to almost 60% of
baseline values by incubation with oxLDL or TNF-. Similarly, DDAH
activity in several tissues was significantly decreased in rabbits fed
a high-cholesterol diet, with no changes in protein
expression. These results are similar to those obtained when
endothelial cells are exposed to
S-2-amino-4(3-methylguanidino) butanoic acid (1
mmol/L), which inhibits DDAH activity and increases the accumulation of
ADMA in the conditioned medium of endothelial
cells.15
ADMA and DDAH are widely distributed in tissues6 and may provide a mechanism for controlling NO synthesis in physiological or pathological states. Our results reveal that lipoproteins or cytokines may increase endothelial elaboration of ADMA by reducing DDAH activity. Decreased activity of DDAH may lead to local accumulation or release of intracellular ADMA and inhibition of NO synthase in disease states, including hypercholesterolemia. The increase in ADMA levels may explain the therapeutic benefit of supplemental L-arginine observed in patients with endothelial dysfunction.16
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Acknowledgments |
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This study was supported in part by a grant from the National Heart, Lung, and Blood Institute (R01 HL-58638). Dr Ito is a recipient of the Japan Heart Foundation and Bayer Yakuhin Research Grant Abroad. Dr Tsao is a recipient of a Scientist Development Grant from the American Heart Association. Dr Cooke is an Established Investigator of the American Heart Association.
Received February 11, 1999; revision received April 1, 1999; accepted April 22, 1999.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–376.[Medline] [Order article via Infotrieve]
2. Cooke JP, Dzau VJ. Derangements of the nitric oxide synthase pathway, L-arginine, and cardiovascular diseases. Circulation. 1997;96:379–382.
3. Vallance P, Leone AM, Calver A, Collier J, Moncada S. Endogenous dimethylarginine as an inhibitor of nitric oxide synthase. J Cardiovasc Pharmacol. 1992;20(suppl 12):560–562.
4.
Kakimoto Y, Akazawa S. Isolation and identification of
NG,
NG- and
NG,
N'G-dimethylarginine,
N
-mono-, di-, and trimethyllysine,
and glucosylgalactosyl-and galactosyl-
-hydroxylysine from human
urine. J Biol Chem. 1970;245:5751–5758.
5. Fickling S, Leone AM, Nussey SS, Vallance P, Whitley GSJ. Synthesis of NG, NG dimethylarginine by human endothelial cells. Endothelium. 1993;1:137–140.
6.
Kimoto M, Whitley GS, Tsuji H, Ogawa T. Detection of
NG,
NG-dimethylarginine
dimethylaminohydrolase in human tissues using a monoclonal antibody.
J Biochem. 1995;117:237–238.
7.
Li H, Oehrlein SA, Wallerath T, Ihrig-Biedevt I,
Wohlfart P, Ulshofer T, Jessen T, Herget T, Forstermann U, Kleinert H.
Activation of protein kinase C alpha and/or epsilon enhances
transcription of the human endothelial nitric oxide
synthase gene. Mol Pharmacol. 1998;53:630–637.
8. Parthasarathy S, Barnett J, Fong LG. High density lipoprotein inhibits oxidative modification of low density lipoprotein. Biochem Biophys Acta. 1990;1044:275–283.[Medline] [Order article via Infotrieve]
9.
Boger RH, Bode-Boger SM, Szuba A, Tsao PS, Chan JR,
Tangphao O, Blaschke TF, Cooke JP. Asymmetric dimethylarginine (ADMA):
a novel risk factor for endothelial dysfunction: its
role in hypercholesterolemia.
Circulation. 1998;98:1842–1847.
10.
Ogawa T, Kimoto M, Sasaoka K. Purification and
properties of a new enzyme, NG,
NG-dimethylarginine
dimethylaminohydrolase, from rat kidney. J Biol Chem. 1989;264:10205–10209.
11. Bode-Boger SM, Boger RH, Kienke S, Junker W, Frolich JC. Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits. Biochem Biophys Res Commun. 1996;219:598–603.[Medline] [Order article via Infotrieve]
12.
Boger RH, Bode-Boger SM, Thiele W, Junker W, Alexander
K, Frolich JC. Biochemical evidence for impaired nitric oxide synthesis
in patients with peripheral arterial occlusive
disease. Circulation. 1997;95:2068–2074.
13.
Kurose I, Wolf R, Grisham MB, Granger DN. Effects of an
endogenous inhibitor of nitric oxide synthesis
on postcapillary venules. Am J Physiol. 1995;268:H2224–H2231.
14.
Faraci FM, Brian JE, Heistad DD. Response of cerebral
blood vessels to an endogenous inhibitor of
nitric oxide synthase. Am J Physiol. 1995;269:H1522–H1527.
15. MacAllister RJ, Parry H, Kimoto M, Ogawa T, Russel RJ, Hodson H, Whitley GSJ, Vallance P. Regulation of nitric oxide synthesis by di-methylarginine dimethylaminohydrolase. Br J Pharmacol. 1996;119:1533–1540.[Medline] [Order article via Infotrieve]
16.
Lerman A, Burnett JC Jr, Higano ST, McKinley LJ, Holmes
DR Jr. Long-term L-arginine supplementation improves
small-vessel coronary endothelial function in
humans. Circulation. 1998;97:2123–2128.
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J. P Cooke ADMA: its role in vascular disease Vascular Medicine, July 1, 2005; 10(1_suppl): S11 - S17. [Abstract] [PDF]
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V.-P. Valkonen, T.-P. Tuomainen, and R. Laaksonen DDAH gene and cardiovascular risk Vascular Medicine, July 1, 2005; 10(1_suppl): S45 - S48. [Abstract] [PDF]
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R. Maas Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA) Vascular Medicine, July 1, 2005; 10(1_suppl): S49 - S57. [Abstract] [PDF]
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T. Teerlink ADMA metabolism and clearance Vascular Medicine, July 1, 2005; 10(1_suppl): S73 - S81. [Abstract] [PDF]
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R. H Boger, E. Schwedhelm, R. Maas, S. Quispe-Bravo, and C. Skamira ADMA and oxidative stress may relate to the progression of renal disease: rationale and design of the VIVALDI study Vascular Medicine, July 1, 2005; 10(1_suppl): S97 - S102. [Abstract] [PDF]
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J. T. Kielstein, S. M. Bode-Boger, G. Hesse, J. Martens-Lobenhoffer, A. Takacs, D. Fliser, and M. M. Hoeper Asymmetrical Dimethylarginine in Idiopathic Pulmonary Arterial Hypertension Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1414 - 1418. [Abstract] [Full Text] [PDF]
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S. Rajagopalan, Q. Sun, and L. C. Chen Particulate Pollution and Endothelial Function: Deja Vu All Over Again in the Air Circulation, June 7, 2005; 111(22): 2869 - 2871. [Full Text] [PDF]
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J. P Cooke ADMA: its role in vascular disease Vascular Medicine, May 1, 2005; 10(2_suppl): S11 - S17. [Abstract] [PDF]
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V.-P. Valkonen, T.-P. Tuomainen, and R. Laaksonen DDAH gene and cardiovascular risk Vascular Medicine, May 1, 2005; 10(2_suppl): S45 - S48. [Abstract] [PDF]
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R. Maas Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA) Vascular Medicine, May 1, 2005; 10(2_suppl): S49 - S57. [Abstract] [PDF]
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T. Teerlink ADMA metabolism and clearance Vascular Medicine, May 1, 2005; 10(2_suppl): S73 - S81. [Abstract] [PDF]
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R. H Boger, E. Schwedhelm, R. Maas, S. Quispe-Bravo, and C. Skamira ADMA and oxidative stress may relate to the progression of renal disease: rationale and design of the VIVALDI study Vascular Medicine, May 1, 2005; 10(2_suppl): S97 - S102. [Abstract] [PDF]
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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]
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V Achan, H. Ho, C Heeschen, M Stuehlinger, J. Jang, M Kimoto, P Vallance, and J. Cooke ADMA regulates angiogenesis: genetic and metabolic evidence Vascular Medicine, February 1, 2005; 10(1): 7 - 14. [Abstract] [PDF]
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A. Tedgui The role of inflammation in atherothrombosis: implications for clinical practice Vascular Medicine, February 1, 2005; 10(1): 45 - 53. [Abstract] [PDF]
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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]
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 R. H. Boger Asymmetric Dimethylarginine, an Endogenous Inhibitor of Nitric Oxide Synthase, Explains the "L-Arginine Paradox" and Acts as a Novel Cardiovascular Risk Factor J. Nutr., October 1, 2004; 134(10): 2842S - 2847S. [Abstract] [Full Text] [PDF]
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R. J. Nijveldt, M. P. C. Siroen, T. Teerlink, and P. A. M. van Leeuwen Elimination of Asymmetric Dimethylarginine by the Kidney and the Liver: A Link to the Development of Multiple Organ Failure? J. Nutr., October 1, 2004; 134(10): 2848S - 2852S. [Abstract] [Full Text] [PDF]
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 K. J. Mather, A. Lteif, H. O. Steinberg, and A. D. Baron Interactions Between Endothelin and Nitric Oxide in the Regulation of Vascular Tone in Obesity and Diabetes Diabetes, August 1, 2004; 53(8): 2060 - 2066. [Abstract] [Full Text] [PDF]
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P. Vallance and J. Leiper Cardiovascular Biology of the Asymmetric Dimethylarginine:Dimethylarginine Dimethylaminohydrolase Pathway Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1023 - 1030. [Abstract] [Full Text] [PDF]
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K. Sydow, B. Hornig, N. Arakawa, S. M Bode-Boger, D. Tsikas, T. Munuzel, and R. H Boger Endothelial dysfunction in patients with peripheral arterial disease and chronic hyperhomocysteinemia: potential role of ADMA Vascular Medicine, May 1, 2004; 9(2): 93 - 101. [Abstract] [PDF]
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J. P. Cooke Asymmetrical Dimethylarginine: The Uber Marker? Circulation, April 20, 2004; 109(15): 1813 - 1818. [Full Text] [PDF]
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E. Ritz and W. M. McClellan Overview: Increased Cardiovascular Risk in Patients with Minor Renal Dysfunction: An Emerging Issue with Far-Reaching Consequences J. Am. Soc. Nephrol., March 1, 2004; 15(3): 513 - 516. [Abstract] [Full Text] [PDF]
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M. Weis, T. N. Kledal, K. Y. Lin, S. N. Panchal, S. Z. Gao, H. A. Valantine, E. S. Mocarski, and J. P. Cooke Cytomegalovirus Infection Impairs the Nitric Oxide Synthase Pathway: Role of Asymmetric Dimethylarginine in Transplant Arteriosclerosis Circulation, February 3, 2004; 109(4): 500 - 505. [Abstract] [Full Text] [PDF]
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J. T. Kielstein, B. Impraim, S. Simmel, S. M. Bode-Boger, D. Tsikas, J. C. Frolich, M. M. Hoeper, H. Haller, and D. Fliser Cardiovascular Effects of Systemic Nitric Oxide Synthase Inhibition With Asymmetrical Dimethylarginine in Humans Circulation, January 20, 2004; 109(2): 172 - 177. [Abstract] [Full Text] [PDF]
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N. Sattar, D. W. McCarey, H. Capell, and I. B. McInnes Explaining How "High-Grade" Systemic Inflammation Accelerates Vascular Risk in Rheumatoid Arthritis Circulation, December 16, 2003; 108(24): 2957 - 2963. [Abstract] [Full Text] [PDF]
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H. Dayoub, V. Achan, S. Adimoolam, J. Jacobi, M. C. Stuehlinger, B.-y. Wang, P. S. Tsao, M. Kimoto, P. Vallance, A. J. Patterson, et al. Dimethylarginine Dimethylaminohydrolase Regulates Nitric Oxide Synthesis: Genetic and Physiological Evidence Circulation, December 16, 2003; 108(24): 3042 - 3047. [Abstract] [Full Text] [PDF]
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 R. J. Nijveldt, T. Teerlink, C. van Guldener, H. A. Prins, A. A. van Lambalgen, C. D. A. Stehouwer, J. A. Rauwerda, and P. A. M. van Leeuwen Handling of asymmetrical dimethylarginine and symmetrical dimethylarginine by the rat kidney under basal conditions and during endotoxaemia Nephrol. Dial. Transplant., December 1, 2003; 18(12): 2542 - 2550. [Abstract] [Full Text] [PDF]
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R. Saran, J. E. Novak, A. Desai, E. Abdulhayoglu, J. S. Warren, R. Bustami, G. J. Handelman, D. Barbato, W. Weitzel, L. G. D'Alecy, et al. Impact of vitamin E on plasma asymmetric dimethylarginine (ADMA) in chronic kidney disease (CKD): a pilot study Nephrol. Dial. Transplant., November 1, 2003; 18(11): 2415 - 2420. [Abstract] [Full Text] [PDF]
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T. Osanai, M. Saitoh, S. Sasaki, H. Tomita, T. Matsunaga, and K. Okumura Effect of Shear Stress on Asymmetric Dimethylarginine Release From Vascular Endothelial Cells Hypertension, November 1, 2003; 42(5): 985 - 990. [Abstract] [Full Text] [PDF]
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R. H Boger The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor Cardiovasc Res, October 1, 2003; 59(4): 824 - 833. [Abstract] [Full Text] [PDF]
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M. M. Engler, M. B. Engler, M. J. Malloy, E. Y. Chiu, M. C. Schloetter, S. M. Paul, M. Stuehlinger, K. Y. Lin, J. P. Cooke, J. D. Morrow, et al. Antioxidant Vitamins C and E Improve Endothelial Function in Children With Hyperlipidemia: Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial Circulation, September 2, 2003; 108(9): 1059 - 1063. [Abstract] [Full Text] [PDF]
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M. S. Post, M. O. Verhoeven, M. J. van der Mooren, P. Kenemans, C. D. A. Stehouwer, and T. Teerlink 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., September 1, 2003; 88(9): 4221 - 4226. [Abstract] [Full Text] [PDF]
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M. C. Stuhlinger, R. K. Oka, E. E. Graf, I. Schmolzer, B. M. Upson, O. Kapoor, A. Szuba, M. R. Malinow, T. C. Wascher, O. Pachinger, et al. Endothelial Dysfunction Induced by Hyperhomocyst(e)inemia: Role of Asymmetric Dimethylarginine Circulation, August 26, 2003; 108(8): 933 - 938. [Abstract] [Full Text] [PDF]
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T. Janatuinen, J. Laakso, R. Laaksonen, R. Vesalainen, P. Nuutila, T. Lehtimaki, O. T Raitakari, and J. Knuuti Plasma asymmetric dimethylarginine modifies the effect of pravastatin on myocardial blood flow in young adults Vascular Medicine, August 1, 2003; 8(3): 185 - 189. [Abstract] [PDF]
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 R P Mookerjee, S Sen, N A Davies, S J Hodges, R Williams, and R Jalan Tumour necrosis factor {alpha} is an important mediator of portal and systemic haemodynamic derangements in alcoholic hepatitis Gut, August 1, 2003; 52(8): 1182 - 1187. [Abstract] [Full Text] [PDF]
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V. Achan, M. Broadhead, M. Malaki, G. Whitley, J. Leiper, R. MacAllister, and P. Vallance Asymmetric Dimethylarginine Causes Hypertension and Cardiac Dysfunction in Humans and Is Actively Metabolized by Dimethylarginine Dimethylaminohydrolase Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1455 - 1459. [Abstract] [Full Text] [PDF]
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J. P. Cooke, K. Sydow, J. Chen, and P. Huang A Peculiar Result and a Fanciful Hypothesis Regarding L-Arginine * Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1128 - 1128. [Full Text] [PDF]
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 D Tousoulis, G J Davies, C Tentolouris, T Crake, G Goumas, C Stefanadis, and P Toutouzas Effects of L-arginine on flow mediated dilatation induced by atrial pacing in diseased epicardial coronary arteries Heart, May 1, 2003; 89(5): 531 - 534. [Abstract] [Full Text] [PDF]
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J. T. Kielstein, S. M. Bode-Boger, J. C. Frolich, E. Ritz, H. Haller, and D. Fliser Asymmetric Dimethylarginine, Blood Pressure, and Renal Perfusion in Elderly Subjects Circulation, April 15, 2003; 107(14): 1891 - 1895. [Abstract] [Full Text] [PDF]
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M. Weis and J. P. Cooke Cardiac Allograft Vasculopathy and Dysregulation of the NO Synthase Pathway Arterioscler Thromb Vasc Biol, April 1, 2003; 23(4): 567 - 575. [Abstract] [Full Text] [PDF]
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S. Ueda, S. Kato, H. Matsuoka, M. Kimoto, S. Okuda, M. Morimatsu, and T. Imaizumi Regulation of Cytokine-Induced Nitric Oxide Synthesis by Asymmetric Dimethylarginine: Role of Dimethylarginine Dimethylaminohydrolase Circ. Res., February 7, 2003; 92(2): 226 - 233. [Abstract] [Full Text] [PDF]
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 M. Knipp, O. Braun, P. M. Gehrig, R. Sack, and M. Vasak Zn(II)-free Dimethylargininase-1 (DDAH-1) Is Inhibited upon Specific Cys-S-Nitrosylation J. Biol. Chem., January 24, 2003; 278(5): 3410 - 3416. [Abstract] [Full Text] [PDF]
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 G. E. Mann, D. L. Yudilevich, and L. Sobrevia Regulation of Amino Acid and Glucose Transporters in Endothelial and Smooth Muscle Cells Physiol Rev, January 1, 2003; 83(1): 183 - 252. [Abstract] [Full Text] [PDF]
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 J. Leiper, J. Murray-Rust, N. McDonald, and P. Vallance S-nitrosylation of dimethylarginine dimethylaminohydrolase regulates enzyme activity: Further interactions between nitric oxide synthase and dimethylarginine dimethylaminohydrolase PNAS, October 15, 2002; 99(21): 13527 - 13532. [Abstract] [Full Text] [PDF]
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A. J. Cardounel and J. L. Zweier Endogenous Methylarginines Regulate Neuronal Nitric-oxide Synthase and Prevent Excitotoxic Injury J. Biol. Chem., September 6, 2002; 277(37): 33995 - 34002. [Abstract] [Full Text] [PDF]
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R. Maas, E. Schwedhelm, J. Albsmeier, and R. H Boger The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function Vascular Medicine, August 1, 2002; 7(3): 213 - 225. [Abstract] [PDF]
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N. Weiss, C. Keller, U. Hoffmann, and J. Loscalzo Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia Vascular Medicine, August 1, 2002; 7(3): 227 - 239. [Abstract] [PDF]
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 H. Masuda, T. Tsujii, T. Okuno, K. Kihara, M. Goto, and H. Azuma Accumulated endogenous NOS inhibitors, decreased NOS activity, and impaired cavernosal relaxation with ischemia Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1730 - R1738. [Abstract] [Full Text] [PDF]
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V. Achan, C. T.L. Tran, F. Arrigoni, G. St.J. Whitley, J. M. Leiper, and P. Vallance all-trans-Retinoic Acid Increases Nitric Oxide Synthesis by Endothelial Cells: A Role for the Induction of Dimethylarginine Dimethylaminohydrolase Circ. Res., April 19, 2002; 90(7): 764 - 769. [Abstract] [Full Text] [PDF]
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M. A.W. Broeders, G. J. Tangelder, D. W. Slaaf, R. S. Reneman, and M. G.A. oude Egbrink Hypercholesterolemia Enhances Thromboembolism in Arterioles but Not Venules: Complete Reversal by L-Arginine Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 680 - 685. [Abstract] [Full Text] [PDF]
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 D. T. Nash Insulin Resistance, ADMA Levels, and Cardiovascular Disease JAMA, March 20, 2002; 287(11): 1451 - 1452. [Full Text] [PDF]
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 R. O. Cannon III Oral L-arginine (and other active ingredients) for ischemic heart disease? J. Am. Coll. Cardiol., January 2, 2002; 39(1): 46 - 48. [Full Text] [PDF]
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J. T. Kielstein, R. H. Boger, S. M. Bode-Boger, J. C. Frolich, H. Haller, E. Ritz, and D. Fliser Marked Increase of Asymmetric Dimethylarginine in Patients with Incipient Primary Chronic Renal Disease J. Am. Soc. Nephrol., January 1, 2002; 13(1): 170 - 176. [Abstract] [Full Text] [PDF]
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M. C. Stuhlinger, P. S. Tsao, J.-H. Her, M. Kimoto, R. F. Balint, and J. P. Cooke Homocysteine Impairs the Nitric Oxide Synthase Pathway: Role of Asymmetric Dimethylarginine Circulation, November 20, 2001; 104(21): 2569 - 2575. [Abstract] [Full Text] [PDF]
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C. Zhang, R. Patel, J. P. Eiserich, F. Zhou, S. Kelpke, W. Ma, D. A. Parks, V. Darley-Usmar, and C. R. White Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1469 - H1475. [Abstract] [Full Text] [PDF]
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H. A. Walker, E. McGing, I. Fisher, R. H. Boger, S. M. Bode-Boger, G. Jackson, J. M. Ritter, and P. J. Chowienczyk Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina: Lack of effect of oral l-arginine on endothelial function, oxidative stress and exercise performance J. Am. Coll. Cardiol., August 1, 2001; 38(2): 499 - 505. [Abstract] [Full Text] [PDF]
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W.-H. Lee, T.-H. Hwang, G. T. Oh, S. U. Kwon, Y.-H. Choi, and J.-E. Park Genetic factors associated with endothelial dysfunction affect the early onset of coronary artery disease in Korean males Vascular Medicine, May 1, 2001; 6(2): 103 - 108. [Abstract] [PDF]
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G. D. Thomas, W. Zhang, and R. G. Victor Nitric Oxide Deficiency as a Cause of Clinical Hypertension: Promising New Drug Targets for Refractory Hypertension JAMA, April 25, 2001; 285(16): 2055 - 2057. [Full Text] [PDF]
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R. H. Boger, S. M. Bode-Boger, P. S. Tsao, P. S. Lin, J. R. Chan, and J. P. Cooke An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2287 - 2295. [Abstract] [Full Text] [PDF]
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G. Wu and C. J. Meininger Arginine Nutrition and Cardiovascular Function J. Nutr., November 1, 2000; 130(11): 2626 - 2629. [Abstract] [Full Text] [PDF]
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J. J. Jang, H.-K. V. Ho, H. H. Kwan, L. F. Fajardo, and J. P. Cooke Angiogenesis Is Impaired by Hypercholesterolemia : Role of Asymmetric Dimethylarginine Circulation, September 19, 2000; 102(12): 1414 - 1419. [Abstract] [Full Text] [PDF]
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J. P. Cooke Does ADMA Cause Endothelial Dysfunction? Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2032 - 2037. [Abstract] [Full Text] [PDF]
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A. Fard, C. H. Tuck, J. A. Donis, R. Sciacca, M. R. Di Tullio, H. D. Wu, T. A. Bryant, N.-T. Chen, M. Torres-Tamayo, R. Ramasamy, et al. 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, September 1, 2000; 20(9): 2039 - 2044. [Abstract] [Full Text] [PDF]
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