Serum Asymmetric Dimethylarginine Concentrations Research Articles

Serum concentration of asymmetric dimethylarginine, inflammatory markers and disease activity in relation with the components of metabolic syndrome in patients with spondyloarthritis

Serum concentration of asymmetric dimethylarginine, inflammatory markers and disease activity in relation with the components of metabolic syndrome in patients with spondyloarthritis

Asymmetric Dimethylarginine (ADMA) in Cardiovascular Disease, Cardiac Ischemia/reperfusion Injury, and Ischemic Non-obstructive Coronary Artery Disease: Biochemical and Pharmacological Implications

: Several studies have shown that high plasma concentrations of asymmetric dimethylarginine (ADMA), a known endogenous competitive inhibitor of endothelial nitric oxide synthase (eNOS), correlate with the severity of coronary artery disease (CAD), with worsening of cardiac ischemia/reperfusion (I/R) injury and coronary atherosclerosis. It is believed that it may be an important risk factor for myocardial infarction. ADMA, when in high concentrations, can determine a significant decrease in the synthesis and bioavailability of NO (Nitric oxide) and therefore alter the mechanisms of regulation of coronary vasodilation and vasomotor function of epicardial coronary arteries. Higher serum ADMA concentration is associated with worsening of post-ischemic remodeling since coronary angiogenesis, vasculogenesis, and collateral coronary growth are seriously impaired. In addition, there are reasons to believe that elevated plasma ADMA levels are related to the development of diseases affecting coronary microcirculation, such as ischemic non-obstructive coronary artery disease (INOCA). With the aim of providing the pharmacologist engaged in the design and discovery of new ADMA-lowering drugs with a complete examination of the subject, in this review, we discuss the most important studies related to the correlations between serum ADMA levels and cardiovascular diseases mentioned above. In addition, we critically discuss the main aspects of enzymology, synthesis, and metabolism of ADMA as a prerequisite for understanding the molecular mechanisms through which high concentrations of ADMA could contribute to promoting cardiovascular diseases. ADMA represents a new target for pharmacological modulation of cardiovascular endothelial function and therefore, there is a possibility of using selective pharmacological ADMA lowering drugs in cardiovascular disease with endothelial dysfunction and high plasma ADMA levels.

The relationship of asymmetric dimethylarginine levels with uncontrolled arterial hypertension and hypertension disease stage

Background: Patients with treatment-resistant hypertension have a worse cardiovascular prognosis compared to those who achieve their target levels of blood pressure (BP). One of biochemical and clinical markers of a decreased response to antihypertensive therapy can be asymmetric dimethylarginine (ADMA), a molecule that reduces formation of nitric oxide and promotes endothelial dysfunction and vasoconstriction.
 Aim: To assess the status of the nitrogen oxide synthesis system and clinical and laboratory profile in patients, depending on the hypertensive disease stage, who achieved or not achieved their target BP levels during hospitalization.
 Materials and methods: We performed аn observational retrospective uncontrolled study in a consecutive sample of 192 patients aged 45–65 years who were admitted to the City Clinical Hospital No. 25 (city of Novosibirsk) with a diagnosis of uncomplicated hypertensive crisis. On the day of discharge, the patients were retrospectively divided into 2 groups. Group 1 included patients who achieved their target BP during hospitalization (target BP group, n = 116). Group 2 included patients with uncontrolled hypertension, in whom the administration of three antihypertensive drugs including a diuretic in optimal or maximal tolerated doses did not result in the achievement of the target BP below 140 and/or 90 mm Hg during hospitalization (non-target BP group, n = 76).
 The following parameters were measured: ADMA, symmetrical dimethylarginine (SDMA), N-monomethyl-L-arginine (NMMA), and total nitric oxide.
 Results: Serum ADMA concentrations (Me [Q25%; Q75%] were increasing with the stage of hypertension: stage I, 0.75 µmol/L [0.66; 0.78], stage II, 1.14 µmol/L [0.87; 1.39], stage III, 1.38 µmol/L [1.22; 1.49] (p 0.0001, Kruskal-Wallis test). In the pairwise comparison, the difference between all these subgroups was significant at p 0.01. In the patients with uncontrolled arterial hypertension ADMA levels were increased compared to those in the target BP group: 1.2 µmol/L [0.99; 1.47] vs 1.07 [0.79; 1.34] µmol/L (p = 0.002). The proportion of patients with type 2 diabetes mellitus among those with uncontrolled arterial hypertension was 31.2% (24/76), while in the target BP group there were only 3.5% of such patients (4/116) (odds ratio 12.57, 95% confidence interval 4.15–38.05; p = 0.00001).
 Conclusion: ADMA measurement may help identify patients with a potential poor response to antihypertensive therapy. This should be taken into account when choosing a treatment regimen and BP monitoring. In addition, ADMA seems to be a promising target for the development of new drug classes.

The role of asymmetric dimethylarginine (ADMA) in COVID-19: association with respiratory failure and predictive role for outcome

We aimed to assess the potential role of Asymmetric dimethylarginine (ADMA) in conditioning respiratory function and pulmonary vasoregulation during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Within 72 h from admission, samples from 90 COVID-19 patients were assessed for ADMA, SDMA, L-arginine concentrations. In addition to classical statistics, patients were also clustered by a machine learning approach according to similar features. Multivariable analysis showed that C-reactive protein (OR 1.012), serum ADMA (OR 4.652), white blood cells (OR = 1.118) and SOFA (OR = 1.495) were significantly associated with negative outcomes. Machine learning-based clustering showed three distinct clusters: (1) patients with low severity not requiring invasive mechanical ventilation (IMV), (2) patients with moderate severity and respiratory failure whilst not requiring IMV, and (3) patients with highest severity requiring IMV. Serum ADMA concentration was significantly associated with disease severity and need for IMV although less pulmonary vasodilation was observed by CT scan. High serum levels of ADMA are indicative of high disease severity and requirement of mechanical ventilation. Serum ADMA at the time of hospital admission may therefore help to identify COVID-19 patients at high risk of deterioration and negative outcome.

Association of serum ADMA, SDMA and L-NMMA concentrations with disease progression in COVID-19 patients.

This study determines and compares the concentrations of arginine and methylated arginine products ((asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), n-monomethyl-1-arginine (L-NMMA) and homoarginine (HA)) for assessment of their association with disease severity in serum samples of COVID-19 patients. Serum arginine and methylated arginine products of 57 mild-moderate and 29 severe (N = 86) COVID-19 patients and 21 controls were determined by tandem mass spectrometry. Moreover, the concentrations of some of the routine clinical laboratory parameters -neutrophil lymphocyte ratio (NLR), C-reactive protein, ferritin, D-dimer, and fibrinogen measured during COVID-19 follow-up were also taken into consideration and compared with the concentrations of arginine and methylated arginine products. Serum ADMA, SDMA and L-NMMA were found to be significantly higher in severe COVID-19 patients, than in both mild-moderate patients and the control group (P < 0.001 for each). In addition, multiple logistic regression analysis indicated L-NMMA (cut-off =120 nmol/L OR = 34, 95% confidence interval (CI) = 3.5-302.0, P= 0.002), CRP (cut-off = 32 mg/L, OR = 37, 95% CI = 4.8-287.0, P < 0.001), and NLR (cut-off = 7, OR = 22, 95% CI = 1.4-335.0, P = 0.020) as independent risk factors for identification of severe patients. The concentration of methylated arginine metabolites are significantly altered in COVID-19 disease. The results of this study indicate a significant correlation between the severity of COVID-19 disease and concentrations of CRP, NLR and L-NMMA.

The impact of type 2 diabetes duration on serum asymmetric dimethylarginine and C-reactive protein concentration in Bosnian patients.

Objective. The present study assessed the impact of type 2 diabetes mellitus (T2DM) duration on the serum asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP) concentration in Bosnian patients. Methods. Participants for this cross-sectional study were randomly selected from the Family Medicine Clinic (Sarajevo, Bosnia and Herzegovina). Serum ADMA concentration was determined by ELISA. Serum high-sensitivity (hs-CRP) was determined by particle-enhanced immunonephelometry. ANOVA test followed by Scheffe post-hoc test or Kruskal-Wallis test followed by Man-Whitney test were used for statistical analysis. Results. The study included 38 patients in up to 10 years diabetes duration (≤10 years T2DM) group, 22 patients in greater than 10 years diabetes duration (>10 years T2DM) group, and 60 controls. Serum ADMA concentration in the >10 years T2DM group (1.81±0.15 μmol/L) was significantly higher compared to serum ADMA concentration in the ≤10 years T2DM group (1.38±0.41 μmol/L; p<0.001) and in controls (0.62±0.15 μmol/L; p<0.001). A significant difference in serum ADMA concentration was found between the <10 years T2DM group and the controls (p<0.001). The serum CRP concentration in the >10 years T2DM group [5.95 (4.20-9.12) mg/L] was significantly higher compared to serum CRP concentration in the <10 years T2DM group [2.35 (1.40-4.30) mg/L; p<0.001] and controls [0.85 (0.50-1.30) mg/L; p<0.001]. Significant difference in serum CRP concentration was observed between the <10 years T2DM group and controls (p<0.001). Conclusions. The present study showed an increase in the serum ADMA and CRP concentrations with the advancement of T2DM. These results suggest that ADMA and CRP may serve as indicators of endothelial dysfunction and chronic low-grade inflammation progression in patients with T2DM. Larger prospective studies are required to confirm the observed findings.

Biomarkers of endothelial dysfunction and atherosclerosis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased prevalence of subclinical atherosclerosis and cardiovascular risk. Angiopoietin-2 (Ang-2), asymmetric dimethylarginine (ADMA), and osteoprotegerin (OPG) are molecules related to endothelial dysfunction (ED) and atherosclerosis, but also to disease severity in patients with chronic inflammatory disorders. In this case-control study, we aimed to investigate serum Ang-2, ADMA, and OPG levels in patients with HS, and to assess the potential relationship between these levels and disease severity. Seventy-five patients with HS and 60 controls were assessed. Serum Ang-2, ADMA, and OPG concentrations were determined in all participants. HS patients had significantly higher Ang-2 and ADMA levels than controls after adjusting for confounders. Besides, Ang-2 concentrations positively correlated with disease severity in the adjusted multivariable analysis. Nevertheless, serum OPG levels did not significantly differ between HS patients and controls. Our results indicate that serum Ang-2 and ADMA levels are significantly increased in patients with HS. Furthermore, Ang-2 might be a suitable marker of HS severity.

Effects of Physical Prehabilitation on the Dynamics of the Markers of Endothelial Function in Patients Undergoing Elective Coronary Bypass Surgery.

Our aim in this study was to evaluate the effect of physical training performed before CABG on the perioperative dynamics of the serum levels of asymmetric dimethylarginine (ADMA) and endothelin-1 (ET-1) of patients with stable coronary heart disease (CHD). Patients in the preoperative period were randomized into two groups: the training group (n = 43) underwent high-intensity treadmill training; the patients in the control group (n = 35) received no training before the procedure. The serum concentrations of ADMA and ET-1 were determined in the perioperative period, and the course of the early postoperative period was analyzed. In the training group, we found a significantly lower incidence of postoperative complications during hospital stays (p = 0.013). At the end of the training program, the ADMA levels were 1.8 times higher in the controls than in the training group (p = 0.001). We found that type 2 diabetes increased the probability of complications by 12 times (OR: 12.3; 95% CI: 1.24–121.5; p = 0.03), as well as elevating the concentration of ET-1 on the eve of surgery (OR: 10.7; 95% CI: 1.4–81.3; p = 0.02). Physical prehabilitation reduced the likelihood of complications nine times (OR: 0.11; 95% CI: 0.02–0.83; p = 0.03). The AUC was 0.851 ± 0.07 (95% CI: 0.71–0.98). The obtained results indicate the benefit of physical training during the prehabilitation stage since it can help to preserve endothelial function.

Association of asymmetric dimethylarginine with the pathological process of persistent pulmonary hypertension of the newborn.

To study the change in asymmetric dimethylarginine (ADMA) in the circulation system of full-term infants with persistent pulmonary hypertension of the newborn (PPHN) and its association with treatment response, as well as the possibility of ADMA as a therapeutic target and a marker for treatment response. A prospective study was performed. A total of 30 full-term neonates who were diagnosed with PPHN within 3 days after birth were enrolled as the PPHN group, and the neonates without PPHN, matched for gestational age and age, who were treated or observed in the department of neonatology were enrolled as the control group. Serum samples were collected on days 1, 7, and 14 of treatment. The high-performance liquid chromatography-tandem mass spectrometry was used to measure the serum concentrations of L-arginine, ADMA, and its isomer symmetric dimethylarginine (SDMA). For the neonates in the control group, the serum concentrations of ADMA and L-arginine continuously increased and the serum concentration of SDMA continuously decreased within the first 14 days of treatment. On days 1 and 14, there was no significant difference in the serum concentration of ADMA between the control and PPHN groups (P>0.05). On day 7, the PPHN group had a significantly higher serum concentration of ADMA than the control group (P<0.05), while there were no significant differences in serum concentrations of SDMA or L-arginine (P>0.05). Moreover, after 7 days of treatment, the PPHN neonates with a systolic pulmonary arterial pressure (sPAP) of >35 mmHg had a significantly higher serum concentration of ADMA than those with an sPAP of ≤35 mm Hg. There are continuous increases in the ADMA concentration and the ADMA/SDMA ratio in the circulation system of full-term infants within the first 2 weeks after birth, and this process is accelerated by the pathological process of PPHN, suggesting that ADMA may be involved in the pathologic process of PPHN. A high level of ADMA is associated with the resistance to PPHN treatment, suggesting that inhibition of ADMA might be a potential target of drug intervention to improve the treatment response of PPHN.

Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation

Mechanical force is critical for the development and remodeling of bone. Here we report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine (ADMA) via regulating the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 (Ddah1) expression in osteoblasts. The presence of -394 4 N del/ins polymorphism of Ddah1 and higher serum ADMA concentration are negatively associated with bone mineral density. Global or osteoblast-specific deletion of Ddah1 leads to increased ADMA level but reduced bone formation. Further molecular study unveils that mechanical stimulation enhances TAZ/SMAD4-induced Ddah1 transcription. Deletion of Ddah1 in osteoblast-lineage cells fails to respond to mechanical stimulus-associated bone formation. Taken together, the study reveals mechanical force is capable of down-regulating ADMA to enhance bone formation.

The relationship of serum asymmetric dimethylarginine concentrations and lung involvement in patients with COVID-19 infection

Aim: COVID-19 infections the tissue through angiotensin converting enzyme 2 receptor, which is also expressed on endothelial cells. Endothelial dysfunction may be associated with lung involvement. Asymmetric dimethylarginine (ADMA) is an indirect marker of endothelial dysfunction. The aim of our study was to evaluate ADMA concentrations and to identify its association with lung involvement in patients with COVID-19 disease. Methods: We included 42 patients with COVID-19 infection and lung involvement (Group 1). Forty-two age and sex matched patients without pneumonia acted as the control group (Group 2). All patients gave blood samples for ADMA at the 1st month control visit after discharge. We compared C-reactive protein (CRP) and ADMA concentrations in addition to routine biochemical parameters between groups. Results: Patients with lung involvement had higher admission glucose, CRP, and ADMA concentrations, and displayed lower hemoglobin concentration and lymphocyte count compared to patients without lung involvement. Although patients with lung involvement had higher ADMA concentrations with respect to those without; plasma ADMA levels were also higher than normal values in control group. Multivariate analysis identified log CRP concentration (OR= 3.047, 95% CI=1.881-5.023, p<0.001) as the independent predictor for lung involvement. And, there was a correlation between ADMA and CRP (r: 0.318, p: 0.003). Conclusion: We revealed elevated ADMA concentrations as the surrogate of endothelial dysfunction in COVID-19 patients whether they have pneumonia or not.

СОСТОЯНИИ СИСТЕМЫ СИНТЕЗА ОКСИДА АЗОТА ПРИ КОМОРБИДНОМ ТЕЧЕНИЕ БРОНХИАЛЬНОЙ АСТМЫ И ГИПЕРТОНИЧЕСКОЙ БОЛЕЗНИ

Comorbidity is a common condition in medical practice. The presence of comorbid conditions in a patient makes a great contribution to the course and prognosis of the underlying disease, as well as the development of complications [12]. At the same time, diseases occurring with broncho-obstructive syndrome and arterial hypertension syndrome are widespread throughout the world [13, 14]. The aim of this study was to assess the degree of endothelial dysfunction associated with impaired nitric oxide synthesis, based on the state of the NO/NOS/ADMA system and genetic polymorphisms of the nitric oxide synthetase gene in patients with bronchial asthma combined with essential hypertension. Materials and methods Three groups of patients, 96 people each, were formed, corresponding in age and gender structure with a diagnosis of bronchial asthma (BA group), essential hypertension (EH group) and their joint course (BA+EH group). Serum concentrations of asymmetric dimethylarginine, symmetric dimethylarginine, genetic polymorphisms of nitric oxide synthase (synthases NOS3 786T/C and NOS3 894G/T) were determined. To determine the role of other factors in increasing the concentration of ADMA and SDMA, multiple linear regression analysis was performed. Results: according to the results of the study, for a group of patients with a combination of bronchial asthma and hypertension, there are increased levels of ADMA and SDMA, the T allele NOS3 786C/T is more common in hypertension, in multiple linear regression significant factors in increasing ADMA are the presence of hypertension, bronchial asthma, body mass index and glomerular filtration rate, for SDMA - the presence of hypertension, asthma and glomerular filtration rate. Conclusions: The comorbidity of bronchial asthma and arterial hypertension is associated with an increased serum concentration of ADMA and SDMA. The presence of the TT genotype of the NOS3 786C/T polymorphism is associated with an increased incidence of arterial hypertension in patients with asthma.

MO1008IMPACT OF RAMIPRIL ON ENDOTHELIAL DYSFUNCTION IN CHILDREN ON REGULAR HEMODIALYSIS

Abstract Background and Aims Endothelial dysfunction is an important risk factor for cardiovascular disease and therefore for increased mortality in end-stage renal disease patients. Asymmetric dimethyl arginine (ADMA), a potent inhibitor of nitric oxide synthase, strongly contributes to endothelial dysfunction. In dialysis patients, ADMA levels are markedly elevated. Previous studies have shown that angiotensin-converting enzyme inhibitors (ACEIs) can significantly reduce ADMA levels in a variety of patients. In contrast, a previous study suggested that short-term treatment with ACEIs may even increase ADMA levels in adult patients on maintenance hemodialysis. However, no study has evaluated the effect of ACEIs in pediatric patients undergoing hemodialysis. Method We conducted a prospective, randomized, double-blinded and placebo-controlled trial (NCT04582097) at two nephrology centers in Cairo, Egypt. Patients below the age of 16 years and on regular hemodialysis for 6 months or longer were eligible for inclusion. Exclusion criteria at screening included uncontrolled hypertension, serum potassium level &amp;gt; 5.5 mmol/L, acute infection or treatment with immunosuppressive agents within the previous month, known intolerance of ACEI treatment and inability to discontinue previous ACEI or angiotensin receptor blocker treatment. A total of 135 eligible patients (mean age, 12.6 years; range 7-15 years; 53.3% males) were randomly (1:1) assigned to once oral daily treatment with identical capsules containing either 2.5 mg ramipril (n=68) or placebo (n=67) for four months. Systolic and diastolic blood pressure (BP) and serum ADMA concentrations were measured as primary efficacy and serum potassium levels as primary safety parameter. Results At baseline, systolic and diastolic BP and ADMA levels were similar between both treatment groups (Table). After four months, both systolic and diastolic BP were significantly lower in the ramipril compared to the placebo group. Treatment with ramipril resulted in a profound reduction in ADMA levels (-77% compared to baseline) while ADMA levels were unchanged in the placebo group after four months (p &amp;lt;0.001). Serum levels of potassium increase in both groups with no reported symptoms of severe hyperkalemia No serious adverse events were reported in neither group. Conclusion Ramipril treatment in pediatric patients on maintenance hemodialysis causes a marked reduction in ADMA levels. This may contribute to improved endothelial vascular function besides its efficacious BP lowering effect.

Asymmetric dimethylarginine in psychiatric disorders

Serum concentrations of asymmetric dimethylarginine (ADMA) in patients with schizophrenia, schizoaffective disorder, bipolar disorder, and depression were determined and compared to serum concentrations in healthy individuals. In all psychiatric diseases investigated, the ADMA concentration was elevated compared to the control group. Patients with recurrent depressive disorder had higher ADMA levels than patients with only one depressive episode. No differences between women and men were found. The elevated ADMA levels suggest that ADMA is involved in the pathophysiology of psychiatric diseases.

Arginine Metabolites as Biomarkers of Myocardial Ischaemia, Assessed with Cardiac Magnetic Resonance Imaging in Chronic Kidney Disease.

(1) Background: Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Myocardial oxygenation and perfusion response to stress, using oxygen-sensitive cardiovascular magnetic resonance (OS-CMR) and stress T1 mapping respectively, are impaired in CKD patients with and without known coronary artery disease (CAD). Endothelial dysfunction, assessed by circulating levels of asymmetric dimethylarginine (ADMA) and homoarginine (HMA), promotes atherosclerosis. We hypothesized that in CKD patients, worsening endothelial dysfunction is associated with worsening myocardial oxygenation and perfusion as assessed by change in OS-CMR signal intensity (Δ OS-CMR SI) and stress T1 (ΔT1) values. (2) Methods: 38 patients with advanced CKD underwent cardiovascular magnetic resonance (CMR) scanning at 3 Tesla. OS-CMR and T1 mapping images were acquired both at rest and after adenosine stress and analyzed semi-quantitatively. Serum ADMA and HMA concentrations were assessed using mass spectrometry. (3) Results: There was no significant correlation between Δ OS-CMR SI and ADMA or HMA. Interestingly, there was a significant negative correlation seen between Δ T1 and ADMA (r = −0.419, p = 0.037, n = 30) but not between Δ T1 and HMA. (4) Conclusions: Stress T1 response is impaired in CKD patients and is independently associated with higher circulating ADMA concentrations.

Altered methylarginine levels after surgery in subjects with multinodular goiter.

Thyroid disorders are important risk factor for cardiovascular diseases. Levels of methylarginines such as asymmetric dimethyl arginine (ADMA), L-monomethyl arginine (L-NMMA), symmetric dimethyl arginine (SDMA) are increase in cardiovascular diseases. Multinodular goiter (MNG) is the most common type of goiter in adults. To date, no study has been conducted to determine the levels of methylarginine in euthyroid MNG patients. Our aim in this study is to compare levels of methylarginines and related metabolites in the preoperative, postoperative MNG patients and controls. Serum ADMA, SDMA, L-NMMA, homoarginine (hArg), arginine and citrulline concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). ADMA (p<0.001), L-NMMA (p=0.002), l-arginine (p=0.006) and citrulline (p<0.001) levels were statistically significantly higher in preop group than postop group. ADMA (p=0.003), L-NMMA (p=0.003) levels were statistically significantly higher and SDMA/ADMA (p<0.001), hArg/ADMA (p<0.001) levels were statistically significantly lower in preop group than control group. The levels of methylarginines and related metabolites altered in the euthyroid MNG patients compared to the control group, and more importantly, there were significant differences between the preop and postop groups. Therefore, these metabolites can be useful in the diagnosis and prognosis of thyroid disorders, even if thyroid hormone levels are normal.

Antepartum and postpartum changes in adipokines, endothelial dysfunction, inflammatory markers and other biochemical parameters in preeclamptic women: A prospective observational cohort study.

This study aimed at evaluating the role played by insulin resistance, lipid metabolism disorder, oxidative stress, resistin, vaspin, Interleukin-18 and asymmetric dimethyl arginine as a marker for endothelial dysfunction in the pathogenesis of preeclampsia. This prospective observational cohort study involved 60 women who were classified into: 20 non-pregnant women (group 1 or control group), 20 normally pregnant women (group 2) and 20 preeclamptic women (group 3) at their third trimester. The pregnant women were assessed at their third trimester and further re-evaluated four weeks after delivery. The assessment included demography, assessment of proteinuria and urinary protein to creatinine ratio, blood pressure measurement and assessment of fasting blood glucose, fasting insulin level, lipid panel and the circulating levels of malondialdehyde, resistin, vaspin, interleukin-18 and asymmetric dimethyl arginine. Preeclamptic women showed more atherogenic lipid profile, significantly higher Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and significantly elevated levels of malondialdehyde, resistin, vaspin and interleukin-18 than the other study groups. Serum asymmetric dimethyl arginine concentration showed non-significant difference among the three study groups. The levels of resistin and vaspin showed significant decrease four weeks postpartum in preeclamptic group. We concluded that, preeclampsia was associated with insulin resistance, dyslipidemia, oxidative stress, inflammation and significant changes in adipokines; resistin and vaspin. Furthermore, the significant increase in the serum levels of resistin and vaspin at the third trimester and their significant decline four weeks postpartum in preeclamptic group focus the attention on the role played by these adipokines in the pathogenesis of preeclampsia.

The Effect and Mechanism of Asymmetric Dimethylarginine Regulating Trophoblastic Autophagy on Fetal Growth Restriction.

Fetal growth restriction (FGR) is an important cause of perinatal death and adverse pregnancy outcomes. Asymmetric dimethylarginine (ADMA) is associated with FGR, but the mechanisms have not been thoroughly studied. Here, we determined the levels of ADMA and autophagy-related molecules in human blood samples and placental tissues. And we also used the human chorionic carcinoma cell line BeWo to investigate the mechanism of ADMA-induced FGR in vitro. Compared with the control group, ADMA levels in maternal blood and placenta were increased in patients with FGR, and the birth weight (BW) percentile was negatively correlated with maternal serum ADMA concentration in the FGR group. The expression of mammalian target of rapamycin (mTOR) in the placenta of the FGR group was lower than the control group, while the expression of Beclin-1 and microtubule-associated protein 1 light chain 3-II (LC3-II)/LC3-I was significantly increased in the FGR group. And the expression of matrix metalloproteinase 9 (MMP9) was decreased in the placenta of patients with FGR. In in vitro cell experiments, compared with the control group, the expression of mTOR and MMP9 in BeWo cells was decreased and the expression of Beclin-1 and LC3-II/LC3-I was increased in the ADMA-treated group. Moreover, ADMA had favorable effects on the formation of autophagic vacuoles, and the autophagy inhibitor 3-Methyladenine (3-MA) could reduce the autophagy-induction effect of ADMA on BeWo cells. This study found that ADMA could participate in the occurrence of FGR through inducing autophagy in trophoblasts.

Correlation of vitamin D and asymmetric dimethylarginine in children with bronchial asthma

ABSTRACT Bronchial Asthma is outlined as a chronic irritation of the airways in children. Vitamin D is a real immune system regulator which has a potential part in allergy. Asymmetric Dimethyl Arginine (ADMA) is an endogenic Nitric Oxide Synthase (NOS) inhibitor. This study is to determine if there is a role of vitamin D deficiency, ADMA in the pathogenesis of asthma in children, And whether the decreased arginine bioavailability and NOS suppression by ADMA contribute to respiratory tract blockage or not. We measured serum vitamin D, ADMA, nitric oxide and plasma L-arginine in 30 asthmatic and 10 healthy children. Serum 25-hydroxy vitamin D, plasma L-Arginine and serum Nitric Oxide were decreased significantly in asthmatic patients compared to healthy children. On the other hand, ADMA serum levels were increased significantly in asthmatic patients. In asthmatic children, there were positive correlations between serum vitamin D concentration and forced expiratory volume in the first, second FEV1 (%predicted). Furthermore, there were negative correlations between serum ADMA concentration and FEV1 (%predicted). In conclusion, marked reduction of vitamin D and elevated ADMA serum levels in asthmatic children has contributed to NOS-related pathophysiology, therefore ADMA and vitamin D could be considered reliable in managing oxidative stress in asthma.

Evaluation of serum neutrophil gelatinase-associated lipocalin (NGAL), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels, and their relations with disease type and activity in inflammatory bowel diseases

Inflammatory bowel disease (IBD) mainly encompass two entities called ulcerative colitis (UC) and Crohn's disease (CD), both of which are chronic, progressive and, inflammatory conditions of the gastrointestinal tract. Various indicators and non-invasive markers have been sought and used in IBD patients to help assessing disease activity and treatment effectiveness although none of them are proven to yield definite results in full correlation with the clinical, endoscopic, and histopathological examinations. The aim of the current study was to investigate the relationship of serum neutrophil gelatinase-associated lipocalin (NGAL), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) levels with disease type and activity and to assess their potential use in establishing diagnosis and activity status of IBD, namely UC and CD. A total of 111 IBD patients with determined active and inactive disease periods and 70 matched controls were recruited. Serum NGAL levels of the patients and the control group were measured using commercially available ELISA kits. ADMA and SMDA levels were measured by high performance liquid chromatography. The IBD group had significantly higher serum levels of NGAL (p = 0.001), ADMA (p = 0.0001), and SDMA (p = 0.0001) in comparison to the control group. Likewise, serum NGAL, ADMA, and SDMA levels were significantly higher in the active IBD group compared to the inactive IBD group (p = 0.0001). Active UC and active CD patients similarly had significantly higher levels of serum NGAL, ADMA, and SDMA than the respective levels in inactive UK and inactive CD patients (p = 0.0001). Serum NGAL, ADMA and SMDA levels are increased in patients with IBD, and serum NGAL, ADMA and SMDA concentrations are significantly higher in active IBD patients than inactive IBD patients. Our results suggest these biomarkers may serve in estimating IBD activity and severity.