Asymmetric dimethylarginine contributes to airway nitric oxide deficiency in patients with <scp>COPD</scp>

Aydın, Murat; Altıntaş, Nejat; Mutlu, Levent Cem; Bilir, Bülent; Oran, Mustafa; Tülübaş, Feti; Topçu, Birol; Tayfur, İsmail; Küçükyalçın, Volkan; Kaplan, Gizem; Gürel, Ahmet

doi:10.1111/crj.12337

Cited by 29 publications

(29 citation statements)

References 33 publications

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“…The lung has been identified as one of the most important sources of ADMA formation;38 however, the role of ADMA in COPD remains unknown yet. Recent studies provide conflicting results, demonstrating either higher39 or lower40 circulating ADMA concentrations in patients with COPD compared with controls. Lower concentrations of ADMA were also found in smokers without COPD compared to nonsmokers 41,42.…”

Section: Discussionmentioning

confidence: 99%

Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD

Urban¹,

Eickhoff²,

Funk³

et al. 2017

COPD

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BackgroundChronic obstructive pulmonary disease (COPD) is associated with an increased cardiovascular risk. However, the mechanisms for this association are yet unclear. The aim of this study was to investigate the relationship between brachial intima-media thickness (B-IMT), an independent predictor of cardiovascular risk, systemic inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in patients with COPD and respective controls.MethodsThe study sample consisted of 60 patients with stable COPD, free from overt cardiovascular disorders, as well as 20 smoking and 20 nonsmoking controls. Ultrasound assessment of B-IMT, spirometry, venous blood sampling for quantification of inflammatory markers and ADMA levels were carried out, and individual cardiovascular risk was calculated via the Framingham risk score.ResultsPatients with COPD showed significantly higher B-IMT compared to smoking (P=0.007) and nonsmoking controls (P=0.033). COPD patients with elevated B-IMT had a twofold increased calculated 10-year risk for cardiovascular events compared to those below the recommended cutoff (P=0.002). B-IMT was significantly associated with systemic inflammation (interleukin-6 [IL-6]; r=0.365, P=0.006) and ADMA (r=0.331, P=0.013) in COPD. Multivariate linear regression revealed male sex and ADMA as independent predictors of B-IMT in this study sample.ConclusionB-IMT is significantly increased in patients with COPD and is associated with systemic inflammation and ADMA levels.

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Section: Discussionmentioning

confidence: 99%

Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD

Urban¹,

Eickhoff²,

Funk³

et al. 2017

COPD

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“…Here, we summarize studies previously reviewed [25,42,43,44,45,46] and highlight new data documenting associations between elevated ADMA levels and clinical conditions in specific patient populations. As shown in Table 1, elevated circulating ADMA concentrations have been described in a variety of diseases across different age and sex groups [3,42,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90]. Differences in ADMA concentrations between sexes are small [33], whereas difference between different age groups do exist.…”

Section: Clinical Conditions Associated With Elevated Adma and Sdmmentioning

confidence: 99%

Toxic Dimethylarginines: Asymmetric Dimethylarginine (ADMA) and Symmetric Dimethylarginine (SDMA)

Tain

Hsu

2017

Toxins

202

195

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Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) are toxic, non-proteinogenic amino acids formed by post-translational modification and are uremic toxins that inhibit nitric oxide (NO) production and play multifunctional roles in many human diseases. Both ADMA and SDMA have emerged as strong predictors of cardiovascular events and death in a range of illnesses. Major progress has been made in research on ADMA-lowering therapies in animal studies; however, further studies are required to fill the translational gap between animal models and clinical trials in order to treat human diseases related to elevated ADMA/SDMA levels. Here, we review the reported impacts of ADMA and SDMA on human health and disease, focusing on the synthesis and metabolism of ADMA and SDMA; the pathophysiological roles of these dimethylarginines; clinical conditions and animal models associated with elevated ADMA and SDMA levels; and potential therapies against ADMA and SDMA. There is currently no specific pharmacological therapy for lowering the levels and counteracting the deleterious effects of ADMA and SDMA. A better understanding of the mechanisms underlying the impact of ADMA and SDMA on a wide range of human diseases is essential to the development of specific therapies against diseases related to ADMA and SDMA.

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“…Results of the two latter patient groups were contrasted with serum ADMA levels of age-matched control groups (0.479±0.06 μmol/L 3 and 0.41 [IQR: 0.38–0.46] μmol/L 6 ). It may be argued that these systemic levels are in the range considered to be normal (0.4–1.0 μmol/L) 3,4,6,8. Regardless, ADMA may assume central importance in the etiopathogenesis of COPD if one considers that serum ADMA levels may be considerably lower than the intracellular levels, while ADMA exerts its above-mentioned effects intracellularly.…”

Section: Discussionmentioning

confidence: 99%

“…The key symptom of COPD is a persistent airflow limitation that progresses over time paralleled by prolonged and abortive inflammatory response in the airways given inhaled irritant particles (eg, smoke)3 and low-grade systemic inflammation 4. Chronic inflammation causes oxidative stress and mostly irreversible structural changes manifested in emphysema and small airway fibrosis,5 both of which lead to persistent and progressive lower airway obstruction, the cause of airflow limitation (and consequent hypoxia) 6.…”

Section: Introductionmentioning

confidence: 99%

Positive correlation of airway resistance and serum asymmetric dimethylarginine level in COPD patients with systemic markers of low-grade inflammation

Tajti¹,

Gesztelyi²,

Pák³

et al. 2017

COPD

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The major feature of COPD is a progressive airflow limitation caused by chronic airway inflammation and consequent airway remodeling. Modified arginase and nitric oxide synthase (NOS) pathways are presumed to contribute to the inflammation and fibrosis. Asymmetric dimethylarginine (ADMA) may shunt L-arginine from the NOS pathway to the arginase one by uncoupling and competitive inhibition of NOS and by enhancing arginase activity. To attest the interplay of these pathways, the relationship between ADMA and airflow limitation, described by airway resistance (Raw), was investigated in a cohort of COPD patients. Every COPD patient willing to give consent to participate (n=74) was included. Case history, laboratory parameters, serum arginine and ADMA, pulmonary function (whole-body plethysmography), and disease-specific quality of life (St George’s Respiratory Questionnaire) were determined. Multiple linear regression was used to identify independent determinants of Raw. The final multiple model was stratified based on symptom control. The log Raw showed significant positive correlation with log ADMA in the whole sample (Pearson’s correlation coefficient: 0.25, P=0.03). This association remained significant after adjusting for confounders in the whole data set (β: 0.42; confidence interval [CI]: 0.06, 0.77; P=0.022) and in the worse-controlled stratum (β: 0.84; CI: 0.25, 1.43; P=0.007). Percent predicted value of forced expiratory flow between 25% and 75% of forced vital capacity showed that significant negative, elevated C-reactive protein exhibited significant positive relationship with Raw in the final model. Positive correlation of Raw with ADMA in COPD patients showing evidence of a systemic low-grade inflammation implies that ADMA contributes to the progression of COPD, probably by shunting L-arginine from the NOS pathway to the arginase one.

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Asymmetric dimethylarginine contributes to airway nitric oxide deficiency in patients with COPD

Abstract: While circulating ADMA is higher, NO is lower in COPD and both show a strong correlation to the degree of airflow limitation. ADMA seems to be a possible new marker of prognosis of COPD and can be a novel therapeutic target for the treatment of COPD.

Cited by 29 publications

References 33 publications

Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD

Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD

Toxic Dimethylarginines: Asymmetric Dimethylarginine (ADMA) and Symmetric Dimethylarginine (SDMA)

Positive correlation of airway resistance and serum asymmetric dimethylarginine level in COPD patients with systemic markers of low-grade inflammation

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