ADMA and hyperhomocysteinemia

2005 ◽  
Vol 10 (1_suppl) ◽  
pp. S27-S33 ◽  
Author(s):  
Sanjana Dayal ◽  
Steven R Lentz
Keyword(s):  
Endothelial Dysfunction ◽  
Molecular Mechanisms ◽  
Asymmetric Dimethylarginine ◽  
Strong Association ◽  
No Synthase ◽  
Endogenous Inhibitor ◽  
Plasma Adma ◽  
Total Homocysteine ◽  
Plasma Total Homocysteine

Hyperhomocysteinemia is a risk factor for cardiovascular disease and stroke. Like many other cardiovascular risk factors, hyperhomocysteinemia produces endothelial dysfunction due to impaired bioavailability of endothelium-derived nitric oxide (NO). The molecular mechanisms responsible for decreased NO bioavailabil ity in hyperhomocysteinemia are incompletely understood, but emerging evidence suggests that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may be a key mediator. Homocysteine is produced during the synthesis of ADMA and can alter ADMA metabolism by inhibiting dimethylarginine dimethy laminohydrolase (DDAH). Several animal and clinical studies have demonstrated a strong association between plasma total homocysteine, plasma ADMA, and endothelial dysfunction. These observations suggest a model in which elevation of ADMA may be a unifying mechanism for endothelial dysfunction during hyper homocysteinemia. The recent development of transgenic mice with altered ADMA metabolism should provide further mechanistic insights into the role of ADMA in hyperhomocysteinemia.

scholarly journals ADMA and hyperhomocysteinemia

2005 ◽  
Vol 10 (2_suppl) ◽  
pp. S27-S33 ◽  
Author(s):  
Sanjana Dayal ◽  
Steven R Lentz
Keyword(s):  
Endothelial Dysfunction ◽  
Molecular Mechanisms ◽  
Asymmetric Dimethylarginine ◽  
Strong Association ◽  
Dimethylarginine Dimethylaminohydrolase ◽  
Plasma Adma ◽  
Total Homocysteine ◽  
No Bioavailability ◽  
Plasma Total Homocysteine

Hyperhomocysteinemia is a risk factor for cardiovascular disease and stroke. Like many other cardiovascular risk factors, hyperhomocysteinemia produces endothelial dysfunction due to impaired bioavailability of endothelium-derived nitric oxide (NO). The molecular mechanisms responsible for decreased NO bioavailability in hyperhomocysteinemia are incompletely understood, but emerging evidence suggests that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may be a key mediator. Homocysteine is produced during the synthesis of ADMA and can alter ADMA metabolism by inhibiting dimethylarginine dimethylaminohydrolase (DDAH). Several animal and clinical studies have demonstrated a strong association between plasma total homocysteine, plasma ADMA, and endothelial dysfunction. These observations suggest a model in which elevation of ADMA may be a unifying mechanism for endothelial dysfunction during hyper-homocysteinemia. The recent development of transgenic mice with altered ADMA metabolism should provide further mechanistic insights into the role of ADMA in hyperhomocysteinemia.

scholarly journals The role of asymmetric dimethylarginine in the development of arterial hypertension.

2018 ◽  
Vol 95 (11) ◽  
pp. 965-970
Author(s):  
V. I. Podzolkov ◽  
T. A. Safronova ◽  
Dinara U. Natkina
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Molecular Mechanisms ◽  
Asymmetric Dimethylarginine ◽  
Biological Marker ◽  
No Production ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor

The results of numerous studies of recent decades confirm the crucial role of vascular endothelium in regulating vascular homeostasis. A plethora of recent studies have shed light on the clinical significance of endothelial dysfunction in essential hypertension. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor. At present, it is considered as a generally recognized marker of endothelial dysfunction by most researchers. In vitro experiments showed that ADMA inhibits endothelium-dependent arterial relaxation, increases the level of indicators characterizing the degree of oxidative stress in endothelial cells, enhances the synthesis of the superoxide anion radical by endothelial cells. The molecular mechanisms described above, activated with an increase in the concentration of ADMA, cause various disturbances in the function of the cardiovascular system, which gave grounds to consider the level of ADMA as a criterion and risk factor for the development of cardiovascular diseases. Thus, ADMA plays a key role in the development and progression of CVD associated with a spectrum of diseases and pathological conditions characterized by a disturbance in NO production. Despite clinical and experimental confirmation of the relationship between the increase in ADMA in plasma and the development of cardiovascular events, the unambiguous etiopathogenetic role of ADMA in CVD requires further research. In order to accurately answer the question of whether ADMA is an etiological factor or a biological marker of CVD, additional analysis is needed to study the biochemical, genetic and pharmacological aspects of ADMA metabolism, the results of which are presented in this article.

scholarly journals DDAH gene and cardiovascular risk

2005 ◽  
Vol 10 (2_suppl) ◽  
pp. S45-S48 ◽  
Author(s):  
Veli-Pekka Valkonen ◽  
Tomi-Pekka Tuomainen ◽  
Reijo Laaksonen
Keyword(s):  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
High Plasma ◽  
No Synthase ◽  
Clinical Role ◽  
Plasma Adma ◽  
Increased Risk ◽  
Major Route

The crucial role of nitric oxide (NO) for normal endothelial function is well known. In many conditions associated with increased risk of cardiovascular diseases such as hypercholesterolemia, hypertension, abdominal obesity, diabetes and smoking, NO biosynthesis is dysregulated, leading to endothelial dysfunction. The growing evidence from animal and human studies indicates that endogenous inhibitors of endothelial NO synthase such as asymmetric dimethylarginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA) are associated with the endothelial dysfunction and potentially regulate NO synthase. The major route of elimination of ADMA is metabolism by the enzymes dimethylarginine dimethylaminohydrolase-1 and -2 (DDAH). In our recent study 16 men with either low or high plasma ADMA concentrations were screened to identify DDAH polymorphisms that could potentially be associated with increased susceptibility to cardiovascular diseases. In that study a novel functional mutation of DDAH-1 was identified; the mutation carriers had a significantly elevated risk for cardiovascular disease and a tendency to develop hypertension. These results confirmed the clinical role of DDAH enzymes in ADMA metabolism. Furthermore, it is possible that more common variants of DDAH genes contribute more widely to increased cardiovascular risk.

scholarly journals Asymmetric Dimethylarginine, C-Reactive Protein, and Carotid Intima-Media Thickness in End-Stage Renal Disease

2002 ◽  
Vol 13 (2) ◽  
pp. 490-496
Author(s):  
Carmine Zoccali ◽  
Francesco Antonio Benedetto ◽  
Renke Maas ◽  
Francesca Mallamaci ◽  
Giovanni Tripepi ◽  
...  
Keyword(s):  
End Stage Renal Disease ◽  
Asymmetric Dimethylarginine ◽  
Intima Media Thickness ◽  
No Synthase ◽  
Endogenous Inhibitor ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Plasma Adma ◽  
Stage Renal Disease ◽  
End Stage

ABSTRACT. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase that has been linked to endothelial dysfunction and atherosclerosis in the general population. ADMA is also elevated in end-stage renal disease and may contribute to the high cardiovascular risk in patients with chronic renal failure. A prospective cohort study was performed to investigate the relationship between plasma ADMA, C-reactive protein (CRP), and intima-media thickness (IMT) in 90 patients undergoing hemodialysis. In the baseline study, plasma ADMA was directly related to IMT both on univariate analysis (r = 0.32, P = 0.002) and on multiple regression analysis (β = 0.23, P = 0.01). In the follow-up study (15 mo) IMT changes were significantly related to ADMA (r = 0.51, P = 0.02) and serum CRP (r = 0.53, P = 0.01) in patients with initially normal IMT. In these patients, ADMA and CRP were strongly interrelated (r = 0.64, P = 0.002), and on multiple regression analysis the interaction between ADMA and CRP emerged as the sole independent predictor of the progression of intimal lesions. Independently of other risk factors, plasma ADMA in patients on hemodialysis is significantly related to IMT. Furthermore, in patients with initially normal IMT, ADMA and CRP are interacting factors in the progression of carotid intimal lesions. These data support the hypothesis that accumulation of this endogenous inhibitor of NO synthase is an important risk factor for cardiovascular disease in chronic renal failure and suggest a possible link between ADMA and inflammation.

scholarly journals Improved blood pressure, nitric oxide and asymmetric dimethylarginine are independent after bariatric surgery

2012 ◽  
Vol 49 (6) ◽  
pp. 589-594 ◽  
Author(s):  
R Patle ◽  
S Dubb ◽  
J Alaghband-Zadeh ◽  
R A Sherwood ◽  
F Tam ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Asymmetric Dimethylarginine ◽  
Obese Patients ◽  
Endogenous Inhibitor ◽  
Nitrite Concentration ◽  
Plasma Adma ◽  
Adma Concentration

Background Obesity is associated with hypertension, but the exact mechanism is not fully understood. Bariatric surgery significantly decreases weight and blood pressure (BP). Low plasma nitric oxide (NO) and raised asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO, concentrations are associated with both obesity and hypertension. Correlations between the changes in these parameters were studied after bariatric surgery. Methods Weight, BP, plasma ADMA and NO were measured in 29 obese patients (24 female, 5 male) before and six weeks after bariatric surgery. Results Patients were 39.2 ± 1.2 (mean ± SEM) years old and weighed 126 ± 3 kg. Six weeks after the surgery, patients had lost 10 ± 0.7 kg ( P < 0.0001) and mean arterial pressure (MAP) decreased by 11 ± 1.0 mmHg ( P < 0.0001). The plasma ADMA concentration decreased by 24 ± 2% from 5 ± 0.4 to 4.0 ± 0.3 μmol/L ( P < 0.0001). The plasma total nitrite concentration increased by 15 ± 1% from 51.4 ± 2.6 to 60 ± 3 μmol/L ( P < 0.0001). The correlation between the decrease of ADMA and increase of NO subsequent to weight loss was significant ( P < 0.0001). However, MAP was not correlated to the changes in ADMA or NO. Conclusions After bariatric surgery, beneficial changes in BP, NO and ADMA occur, but our findings suggest that these BP changes are independent of changes in the NO–ADMA axis. Other causes for the changes in BP should therefore be considered.

scholarly journals DDAH gene and cardiovascular risk

2005 ◽  
Vol 10 (1_suppl) ◽  
pp. S45-S48 ◽  
Author(s):  
Veli-Pekka Valkonen ◽  
Tomi-Pekka Tuomainen ◽  
Reijo Laaksonen
Keyword(s):  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
High Plasma ◽  
No Synthase ◽  
Clinical Role ◽  
Plasma Adma ◽  
Increased Risk ◽  
Major Route ◽  
Increased Susceptibility

The crucial role of nitric oxide (NO) for normal endothelial function is well known. In many conditions associated with increased risk of cardiovascular diseases such as hypercholesterolemia, hypertension, abdominal obesity, diabetes and smok ing, NO biosynthesis is dysregulated, leading to endothelial dysfunction. The grow ing evidence from animal and human studies indicates that endogenous inhibitors of endothelial NO synthase such as asymmetric dimethylarginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA) are associated with the endothelial dysfunc tion and potentially regulate NO synthase. The major route of elimination of ADMA is metabolism by the enzymes dimethylarginine dimethylaminohydrolase-1 and -2 (DDAH). In our recent study 16 men with either low or high plasma ADMA concen trations were screened to identify DDAH polymorphisms that could potentially be associated with increased susceptibility to cardiovascular diseases. In that study a novel functional mutation of DDAH-1 was identified; the mutation carriers had a significantly elevated risk for cardiovascular disease and a tendency to develop hypertension. These results confirmed the clinical role of DDAH enzymes in ADMA metabolism. Furthermore, it is possible that more common variants of DDAH genes contribute more widely to increased cardiovascular risk.

scholarly journals Concentrations of the Selected Biomarkers of Endothelial Dysfunction in Response to Antiepileptic Drugs: A Literature Review

2019 ◽  
Vol 25 ◽  
pp. 107602961985942 ◽  
Author(s):  
Beata Sarecka-Hujar ◽  
Izabela Szołtysek-Bołdys ◽  
Ilona Kopyta ◽  
Barbara Dolińska ◽  
Andrzej Sobczak
Keyword(s):  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Literature Review ◽  
Antiepileptic Drug ◽  
Asymmetric Dimethylarginine ◽  
The Body ◽  
Biochemical Processes ◽  
The Brain

Epilepsy is a disease arising from morphological and metabolic changes in the brain. Approximately 60% of patients with seizures can be controlled with 1 antiepileptic drug (AED), while in others, polytherapy is required. The AED treatment affects a number of biochemical processes in the body, including increasing the risk of cardiovascular diseases (CVDs). It is indicated that the duration of AED therapy with some AEDs significantly accelerates the process of atherosclerosis. Most of AEDs increase levels of homocysteine (HCys) as well as may affect concentrations of new, nonclassical risk factors for atherosclerosis, that is, asymmetric dimethylarginine (ADMA) and homoarginine (hArg). Because of the role of these parameters in the pathogenesis of CVD, knowledge of HCys, ADMA, and hArg concentrations in patients with epilepsia treated with AED, both pediatric and adult, appears to be of significant importance.

Molecular Mechanisms of Endothelial Dysfunction in the Insulin-Resistant State: the Roles of Abnormal Pteridine Metabolism

Pteridines ◽  
2003 ◽  
Vol 14 (1) ◽  
pp. 13-16
Author(s):  
Kazuya Shinozaki ◽  
Atsunori Kashiwagi ◽  
Masahiro Masada ◽  
Tomio Okamura
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Molecular Mechanisms ◽  
No Synthase ◽  
Oral Supplementation ◽  
Insulin Resistant ◽  
Underlying Mechanisms ◽  
Vascular Oxidative Stress ◽  
Resistant State ◽  
Insulin Resistant State

Abstract Although abnormalities in endothelial function are described in various insulin-resistant conditions, including obesity, diabetes, and hypertension in both humans and animal models, the underlying mechanisms are poorly understood. Experimental evidence suggests that (6R)-5,6,7,8-tetrahydrobiopterin (BH4), the natural and essential cofactor of NO synthases (NOS), plays a crucial role not only in increasing the rate of NO generation by NOS bat also in Controlling the formation of superoxide anion (O2 ) in endothelial cells. Under insulin-resistant conditions where BH4 levels are suboptimal, the production of O2 by NO synthase leads to endothelial dysfunction. Furthermore, oral supplementation of BH4 (10 mg/kg/day) for 8 weeks restores endothelial function and relieved oxidative tissue damage, at least in part, through activation of eNOS in the aorta of insulin-resistant rats. These results suggest that abnormal pteridine metabolism contributes to causing endothelial dysfunction and the enhancement of vascular oxidative stress in the insulin-resistant State.

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