The biochemistry, measurement and current clinical significance of asymmetric dimethylarginine

Blackwell, Scott

doi:10.1258/acb.2009.009196

Cited by 68 publications

(74 citation statements)

References 139 publications

(225 reference statements)

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“…This is susceptible to oxidation as a consequence of oxidative stress and may provide a mechanism that results in increased ADMA concentration and reduced NO formation [37]. This has been observed with hyperglycaemia and hyperhomocystinaemia [37]. Therefore, interaction between dimethylaminohydrolase (DDAH), ADMA and NOS may present a common pathway of several risk factors affecting the vascular endothelium.…”

Section: Discussionmentioning

confidence: 99%

“…ADMA has been implicated in the endothelial dysfunction accompanying a broad range of clinical disorders such as obesity, cardiovascular disease, chronic renal failure, diabetes and hypertension [7][8][9]. Indeed, a significant increase in plasma ADMA concentration has been reported in individuals with impaired glucose tolerance [10], diabetes [11] and in the overweight, in whom weight loss was associated with a reduction in ADMA and improved markers of insulin sensitivity [10].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of asymmetrical dimethylarginine metabolism in patients with critical illness

Ghashut

Blackwell

Ryan

et al. 2017

Eur J Clin Investigation

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Background: Critically ill patients experience metabolic disorders including hypercatabolic state and hyperglycaemia and these are associated with poor outcome. Hyperglycaemia and asymmetric dimethylarginine (ADMA) are reported to have significant influences on endothelial dysfunction. The aim of the present study was to examine the relationship between plasma asymmetric dimethylarginine (ADMA) and related arginine metabolism in patients with critical illness.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Assessment of asymmetrical dimethylarginine metabolism in patients with critical illness

Ghashut

Blackwell

Ryan

et al. 2017

Eur J Clin Investigation

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“…15 Degradation of ADMA is mediated principally by dimethylarginine dimethylaminohydrolase (DDAH). It has been proposed that the elevation in plasma ADMA that occurs with vascular disease is largely due to impaired activity of DDAH.…”

Section: Introductionmentioning

confidence: 99%

The cardiovascular risk marker asymmetric dimethylarginine is elevated in asymptomatic, untreated HIV-1 infection and correlates with markers of immune activation and disease progression

2013

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Background: As lifespan in HIV infection increases, cardiovascular disease has emerged as a cause of morbidity and mortality. Asymmetric dimethylarginine is an established marker of endothelial dysfunction and predicts cardiovascular events. The role of asymmetric dimethylarginine in HIV-related cardiovascular disease has not been established. Our aim was to determine whether asymmetric dimethylarginine concentrations were elevated in treatment naïve, HIV-infected subjects and to correlate these with markers of immune activation and disease progression. Methods: Serum samples were collected from HIV-positive and -negative subjects attending a primary health care clinic over a 12-month period. Asymmetric dimethylarginine concentrations were measured and correlated with CD4 count, viral load, hsCRP, IL-6, IgG, adenosine deaminase and CD8/38 T lymphocytes. Results: Sixty HIV-positive participants (mean age 32.0 years) and 20 HIV-negative controls (mean age 32.4 years) were studied. All were of black ethnicity. The mean asymmetric dimethylarginine concentration in the infected group measured 0.67 mmol/L (95% CI 0.62-0.72 mmol/L) which was significantly higher than in the control group of 0.48 mmol/L (95% CI 0.40-0.56 mmol/L). Asymmetric dimethylarginine correlated inversely with CD4 counts and positively with IgG, adenosine deaminase and CD8/38 T lymphocytes. No significant correlation was found with hsCRP, IL-6, or viral load. Conclusion: We demonstrated that asymmetric dimethylarginine is elevated in HIV infection, in patients with relatively well-preserved CD4 counts not yet on anti-retroviral treatment. We showed significant correlations of asymmetric dimethylarginine with CD8/38 T lymphocytes, IgG and adenosine deaminase, suggesting that T-cell activation and the adaptive immune response underlie asymmetric dimethylarginine elevation in this population.

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“…These biomarkers include plasma/serum concentrations of B vitamins (folate, cobalamin, vitamins B2 and B6) (8 ), methylamines (choline, betaine, dimethylglycine) (9 ), metabolites (total homocysteine, methylmalonic acid) reflecting B vitamin status in tissues (10 ), methylarginines linked to endothelial function (11 ), and tryptophan metabolites along the kynurenine pathway (12 ), which depends on both vitamin B6 and B2.…”

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confidence: 99%

Kinetic Modeling of Storage Effects on Biomarkers Related to B Vitamin Status and One-Carbon Metabolism

et al. 2012

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BACKGROUND Biomarkers and metabolites related to B vitamin function and one-carbon metabolism have been studied as predictors of chronic diseases in studies based on samples stored in biobanks. For most biomarkers, stability data are lacking or fragmentary. METHODS Degradation and accumulation kinetics of 32 biomarkers were determined at 23 °C in serum and plasma (EDTA, heparin, and citrate) collected from 16 individuals and stored for up to 8 days. In frozen serum (−25 °C), stability was studied cross-sectionally in 650 archival samples stored for up to 29 years. Concentration vs time curves were fitted to monoexponential, biexponential, linear, and nonlinear models. RESULTS For many biomarkers, stability was highest in EDTA plasma. Storage effects were similar at room temperature and at −25 °C; notable exceptions were methionine, which could be recovered as methionine sulfoxide, and cystathionine, which decreased in frozen samples. Cobalamin, betaine, dimethylglycine, sarcosine, total homocysteine, total cysteine, tryptophan, asymetric and symmetric dimethyl argenine, creatinine, and methylmalonic acid were essentially stable under all conditions. Most B vitamins (folate and vitamins B2 and B6) were unstable; choline increased markedly, and some amino acids also increased, particularly in serum. The kynurenines showed variable stability. For many biomarkers, degradation (folate and flavin mononucleotide) or accumulation (pyridoxal, riboflavin, choline, amino acids) kinetics at room temperature were non–first order. CONCLUSIONS Data on stability and deterioration kinetics for individual biomarkers are required to optimize procedures for handling serum and plasma, and for addressing preanalytical bias in epidemiological and clinical studies.

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The biochemistry, measurement and current clinical significance of asymmetric dimethylarginine

Cited by 68 publications

References 139 publications

Assessment of asymmetrical dimethylarginine metabolism in patients with critical illness

Assessment of asymmetrical dimethylarginine metabolism in patients with critical illness

The cardiovascular risk marker asymmetric dimethylarginine is elevated in asymptomatic, untreated HIV-1 infection and correlates with markers of immune activation and disease progression

Kinetic Modeling of Storage Effects on Biomarkers Related to B Vitamin Status and One-Carbon Metabolism

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