Asymmetric Dimethylarginine Concentrations Research Articles

Homocysteine and Asymmetric Dimethylarginine (ADMA) in Neurological Diseases

Homocysteine (Hcy) is formed from methionine (Met) and is distributed in two metabolic pathways: in the process of remethylation to Met and in the process of transsulfuration to cysteine. Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular and neurological diseases such as: Alzheimer’s and Parkinson’s diseases, multiple sclerosis, and stroke. Increased Hcy level may lead to endothelial dysfunction due to impaired bioavailability of endothelium-derived nitric oxide (NO). The molecular mechanism decreasing the levels of NO in HHcy conditions is incompletely understood, but it seems that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may be a key factor. ADMA is formed from L-arginine by enzymes in the family of protein N-methyltransferases (PRMT) and may undergo hydrolysis to L-citrulline and dimethylamine with the participation of dimethylaminohydrolase (DDAH). In pathological conditions such as neurodegenerative diseases, Hcy may lead to increased ADMA concentrations by inhibiting the activity of DDAH. Several drugs, such L-dopa, antiepileptic drugs, and lipid-lowering drugs, may interfere with the metabolic pathways of thiols, leading to an alteration of plasma Hcy and ADMA levels. It seems that administration of L-arginine, in conjunction with B vitamins, to patients with HHcy may be a new method in the treatment of neurodegenerative diseases.

Asymmetric dimethylarginine and arginine metabolites in women with and without a history of gestational diabetes

AimsDysregulation of arginine metabolism, as evidenced by increased circulating levels of asymmetric dimethylarginine (ADMA), has been proposed as an early event in the natural history of cardiovascular disease. Since the diagnosis of gestational diabetes mellitus (GDM) identifies a patient population at increased future risk of cardiovascular disease later in life, we sought to characterize arginine metabolism in women with and without a history of recent GDM. MethodsIn this prospective observational cohort study, 225 women (72 who had GDM; 153 who did not) underwent cardiometabolic characterization, including oral glucose tolerance test, at 1- and 3-years postpartum. Circulating ADMA and its stereoisomer symmetric dimethylarginine (SDMA) were measured by liquid chromatography–mass spectrometry at both visits. ResultsSerum ADMA and SDMA were not significantly different between the GDM and non-GDM groups at either 1-year or 3-years postpartum. On multiple linear regression analyses, high-density-lipoprotein cholesterol (t=−2.62, p=0.009) and creatinine (t=−2.62, p=0.01) were independently associated with ADMA at 3-years, while creatinine (t=7.09, p<0.0001) and BMI (t=−2.24, p=0.026) predicted SDMA. ConclusionWomen with recent GDM do not exhibit altered serum concentrations of ADMA or SDMA at 1- and 3-years postpartum, suggesting that ADMA dysregulation is not a feature of their cardiometabolic profile in the early years after delivery.

The role of L-arginine/L-homoarginine/nitric oxide pathway for aortic distensibility and intima-media thickness in stroke patients.

Asymmetric dimethylarginine (ADMA) and L-homoarginine (hArg) are L-arginine (Arg) metabolites derived from different pathways. Protein arginine N-methyltransferase (PRMT) and subsequent proteolysis of proteins containing methylarginine residues release ADMA. Arginine:glycine amidinotransferase (AGAT) converts Arg to hArg and guanidinoacetate (GAA). While high concentrations of ADMA and low concentrations of hArg in the blood have been established as cardiovascular risk markers, the cardiovascular relevance of GAA is still unexplored. Arg and hArg are substrates and ADMA is an inhibitor of nitric oxide (NO) synthase (NOS). The cardiovascular effects of ADMA and hArg have been related to NO, a potent endogenous vasodilator. ADMA and hArg are considered to exert additional, not yet explored, presumably NO-unrelated effects and to act antagonistically in the renal and cardiovascular systems. Although the physiological role of Arg, ADMA, hArg and NO for endothelial function in small- and medium-sized arteries has been intensively studied in the past, the clinical relevance of aortic wall remodeling still remains unclear. Here, we evaluated potential relation between aortic distensibility (AD) or aortic intima-media thickness (aIMT) and circulating ADMA, hArg, GAA, and the NO metabolites nitrite and nitrate in the plasma of 78 patients (24 females, 54 males; aged 59±14years) with recent ischemic stroke or transient ischemic attack (TIA). All biochemical parameters were determined by stable-isotope dilution gas chromatography-mass spectrometry. AD and aIMT were measured by transesophageal echocardiography. Arg, hArg, ADMA and GAA median plasma concentrations (µM) were determined to be 61, 1.43, 0.50 and 2.16, respectively. hArg, ADMA and GAA correlated closely with Arg. Nitrite, nitrate and creatinine median plasma concentrations (µM) were 2.49, 48.7, and 84.1, respectively. Neither AD (2.61 vs. 1.8510-6 × cm2×dyn-1, P=0.064) nor aIMT (1.25 vs. 1.13mm, P=0.596) differed between females and males. The hArg/ADMA molar ratio (r=-0.351, P=0.009), nitrate (r=0.364, P=0.007) and nitrite (r=0.329, P=0.015) correlated with aIMT but not with AD. Arg, hArg, ADMA and GAA correlated with aIMT but not with AD. The results demonstrate a strong relation between the Arg/NO pathway and aortic atherosclerosis but not with AD suggesting different mechanisms underlying the two aspects of aortic wall remodeling.

Evaluation of ADMA, carbonyl groups, CAT and NKA in depressed patients with and without posttraumatic stress disorder.

It has been shown that asymmetric dimethylarginine (ADMA), carbonyl groups, catalase (CAT) and neurokinin A (NKA) are actively involved in neuronal processes such as depression and posttraumatic stress disorder (PTSD). One of their roles is to protect the body from oxidative damage. This is done by affecting neuronal growth, development and plasticity. The study aimed at assessing the concentrations of ADMA, carbonyl groups, CAT and NKA in patients with varying levels of depression severity, PTSD, and depression concurrent with PTSD. The study covered 460 people. Out of them, 120 suffered from different types of depression. The study groups comprised: 60 subjects with mild depression (MD), 60 subjects with moderate depression (MOD), 60 subjects with severe depression (SeD), 60 subjects with MD and PTSD (MD+PTSD), 60 subjects with MOD and PTSD (MOD+PTSD), 60 subjects with SeD and PTSD (SeD+PTSD), and 60 subjects with PTSD alone. Each group of 60 participants included 30 males and 30 females. The concentrations of all blood parameters were determined at 7 a.m. using the ELISA method. Depressive episodes became more severe as the concentration levels of studied markers increased. ADMA, carbonyl groups, CAT and NKA can be useful markers of chronic stress in both males and females with depression, PTSD, and depression concurrent with PTSD. They can be utilized when making an initial diagnosis and evaluating the severity of disease. Changes in their concentration levels may show a biological response to oxidative stress characteristic of depression.

Comprehensive analysis of the L-arginine/L-homoarginine/nitric oxide pathway in preterm neonates: potential roles for homoarginine and asymmetric dimethylarginine in foetal growth.

L-Arginine (Arg) and L-homoarginine (hArg) are precursors of nitric oxide (NO), a signalling molecule with multiple important roles in human organism. In the circulation of adults, high concentrations of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) and low concentrations of hArg emerged as cardiovascular risk factors. Yet, the importance of the Arg/hArg/NO pathway, especially of hArg and ADMA, in preterm neonates is little understood. We comprehensively investigated the Arg/hArg/NO pathway in 106 healthy preterm infants (51 boys, 55 girls) aged between 23+6 and 36+1 gestational weeks. Babies were divided into two groups: group I consisted of 31 babies with a gestational age of 23+6 - 29+6weeks; group II comprised 75 children with a gestational age of 30+0 - 36+1weeks. Plasma and urine concentrations of ADMA, SDMA, hArg, Arg, dimethylamine (DMA) which is the major urinary ADMA metabolite, as well as of nitrite and nitrate, the major NO metabolites, were determined by GC-MS and GC-MS/MS methods. ADMA and hArg plasma levels, but not the hArg/ADMA molar ratio, were significantly higher in group II than in group I: 895±166nM vs. 774±164nM (P=0.001) for ADMA and 0.56±0.04µM vs. 0.48±0.08µM (P=0.010) for hArg. There was no statistical difference between the groups with regard to urinary ADMA (12.2±4.6 vs 12.8±3.6µmol/mmol creatinine; P=0.61) and urinary SDMA. Urinary hArg, ADMA, SDMA correlated tightly with each other. Urinary excretion of DMA was slightly higher in group I compared to group II: 282±44 vs. 247±35µmol/mmol creatinine (P=0.004). The DMA/ADMA molar ratio in urine was tendentiously higher in neonates of group I compared to group II: 27±13 vs. 20±5 (P=0.065). There were no differences between the groups with respect to Arg in plasma and to nitrite and nitrate in plasma and urine. In preterm neonates, ADMA and hArg biosynthesis increases with gestational age without remarkable changes in the hArg/ADMA ratio or NO biosynthesis. Our study suggests that ADMA and hArg are involved in foetal growth.

Preservation of vascular DDAH activity contributes to the protection of captopril against endothelial dysfunction in hyperlipidemic rabbits

Endothelial dysfunction plays a pivotal role in the pathogenesis of atherosclerosis. Endogenous inhibitor of nitric oxide synthase (NOS) asymmetric dimethylarginine (ADMA) has been recognized as an independent risk factor of endothelial dysfunction and the biomarker of atherosclerosis. This study was to investigate whether endogenous ADMA and its metabolic enzyme dimethylarginine dimethylaminohydrolase (DDAH) were involved in mechanisms of captopril protection against endothelial dysfunction in high fat diet feeding rabbits. Half of model rabbits were treated with captopril (10mg/kg/d, i.g.) for 12w. Vascular morphology and serum lipid profiles were detected. Serum ADMA concentration were assayed by high performance liquid chromatography. Recombinant DDAH2 gene adenoviruses were ex vivo transferred to thoracic aortas of high fat diet feeding rabbits. Endothelium-dependent relaxation of aortas response to acetylcholine and DDAH activity were measured. Atherosclerosis was confirmed in high fat diet feeding rabbits by increased serum lipid profiles and morphologic changes of vascular wall. Serum ADMA levels were significantly increased in hyperlipidemic rabbits accompanied with impairment of endothelium-dependent relaxation and inhibition of DDAH activity in thoracic aortas. Captopril treatment not only decreased vascular intima thickening and serum ADMA concentration but also preserved vascular DDAH activity and endothelium-dependent relaxation in hyperlipidemic rabbits without influence on serum lipid profiles. Similar beneficial effects on endothelial function and DDAH activity could be achieved by DDAH2 gene transfection. These results indicated that captopril could protect against injuries of vascular morphology and endothelial function in hyperlipidemic rabbits, the mechanisms may be related to the preservation of DDAH activity and decrease of ADMA accumulation in vascular endothelium.

Endothelial dysfunction in the early postoperative period after major colon cancer surgery

BackgroundEvidence suggests that endothelial dysfunction in the early postoperative period promotes myocardial injury after non-cardiac surgery. The aim of this study was to investigate the impact of colon cancer surgery on endothelial function and the association with the l-arginine-nitric oxide pathway postoperatively. MethodsPatients undergoing elective colon cancer surgery (n = 31) were included in this prospective observational cohort study. Endothelial function, as measured using the reactive hyperaemia index (RHI), was assessed non-invasively using digital pulse tonometry. RHI and plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), dihydrobiopterin and biopterin metabolites, tetrahydrobiopterin (BH4) and total biopterin were measured before surgery, at four h after surgery and at postoperative day one and two. Cardiac troponin I was measured before surgery and once daily on postoperative days one to four. ResultsPreoperative RHI was 1.86 (1.64 – 2.11) and decreased significantly during the observation period (linear mixed effects model of serial measurements, P = 0.015). Both L-arginine (P < 0.001) and ADMA (P = 0.024) decreased during the postoperative period. All biopterin metabolites were significantly decreased after surgery. A significant positive correlation was found between logAUC(l-arginine/ADMA) and logAUC(RHI) (P = 0.015) and between logAUC(L-arginine/ADMA) and logAUC(BH4) (P = 0.015). None of the patients had cardiac troponin I elevations. ConclusionsRHI was attenuated in the first days after colon cancer surgery indicating acute endothelial dysfunction. Endothelial dysfunction correlated with disturbances in the L-arginine – nitric oxide pathway. Our findings provide a rationale for investigating the hypothesized association between acute endothelial dysfunction and cardiovascular complications after non-cardiac surgery. Clinical trial registrationNCT02344771.

Asymmetric Dimethylarginine Induced Apoptosis and Dysfunction of Endothelial Progenitor Cells: Role of Endoplasmic Reticulum Stress Pathway.

Asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, is a novel risk factor of cardiovascular disease. Endothelial progenitor cells (EPCs) bear typical endothelial characteristics and are thought to contribute to neovascularization by providing new endothelial cells (ECs) after arterial injury. Many studies have shown that ADMA can induce EPC apoptosis and dysfunction, but the underlying mechanism is not well understood. EPCs from umbilical cord blood were cultured in EGM-2 medium with particular growth factors and supplemented with 10% fetal bovine serum. The cells were treated with different concentrations of ADMA (5, 10, and 50 μmol/L). Endoplasmic reticulum (ER) stress marker levels were examined by western blot analysis. After 24-hour incubation, ADMA induced apoptosis of EPCs and significantly decreased the proliferation, migration, and vasculogenesis capacity of EPCs. We also found that ADMA treatment activated phosphorylated protein kinase RNA-activated-like ER kinase (PERK), a stress sensor protein in the endoplasmic reticulum (ER). The activated PERK induced 78 kDa glucose-regulated protein (GRP-78) and C/EBP homologous protein (CHOP) expression. Additionally, the inhibition of the ER stress pathway by Salubrinal (a specific ER stress inhibitor) can attenuate ADMA-induced apoptosis of EPCs. Overall, these observations indicate that ADMA may induce the apoptosis and dysfunction of EPCs through the ER stress pathway.

Asymmetric dimethylarginine and M30 concentrations in heart failure

Asymmetric dimethylarginine and M30 concentrations in heart failure

Plasma Apelin and Asymmetric Dimethylarginine (ADMA) Levels Shortly After Laparoscopic Greater Curvature Plication.

We sought to investigate the short-term effect of weight loss following restrictive bariatric surgery on plasma concentrations of apelin and asymmetric dimethylarginine (ADMA) in individuals with morbid obesity. Thirty-seven morbidly obese individuals underwent laparoscopic greater curvature plication (LGCP). Anthropometric indices and plasma concentrations high-sensitivity C-reactive protein (hsCRP), apelin, and ADMA were measured before and 6weeks after LGCP. The percentage of total weight loss was 12.9±4.4% 6weeks after the operation. ADMA and apelin levels decreased significantly (p<0.001 and 0.032, respectively) following LGCP. Significant decrements occurred in weight, body mass index, waist and hip circumference (p<0.001), and waist-to-hip ratio (p=0.013). The levels of triglycerides (p=0.017), low-density lipoprotein cholesterol (p=0.020), fasting plasma glucose (p=0.033), fasting plasma insulin (p=0.042), and the homeostasis model assessment index of insulin resistance (p=0.034) also significantly decreased compared to the baseline measures. No significant change was observed in hsCRP levels and systolic and diastolic blood pressures. There was no significant correlation between changes in levels of apelin or ADMA and changes in anthropometric indices and other laboratory parameters. Surgically induced weight loss rapidly decreases plasma levels of ADMA and apelin in morbidly obese patients. These changes do not seem correlated with changes in anthropometric and laboratory parameters associated with obesity.

The influence of renin angiotensin aldosterone system blockers on asymmetric dimethylarginine levels in patients with chronic glomerulonephritis

AbstractEndothelial dysfunction could be related to the limited availability of nitric oxide (NO). NO is synthesized with the participation of an NO synthase whose activity is inhibited by asymmetric dimethylarginine (ADMA). The synthesis of ADMA is exacerbated by oxidative stress, and several studies have shown the efficacy of drugs acting on the renin-angiotensin-aldosterone system (RAAS) (converting enzyme inhibitors and angiotensin II receptor antagonists) in reducing the level of ADMA. The probable mechanism of drug action is a reduction of oxidative stress through a decrease of angiotensin II formation. The aim of this study was to assess the influence of RAAS blockers on the plasma concentration of ADMA in patients with chronic glomerulonephritis (ChGN). The study included 37 patients, placed into group A and group B, depending on the treatment. Both groups were treated with RAAS blockers. In group B, immunosuppressive drugs were additionally administered. The control visits were at the 0, 6 and 12 months of observation. In both the studied groups (A+B), a significant reduction of ADMA (0.77 vs 0.4 μmol/l; p&lt;0.05) was noticed. In patients suffering from ChGN, the use of RAAS blockers resulted in a significant decrease of plasma ADMA concentration, independently of immunosupressive treatment.

Increased serum concentrations of asymmetric dimethylarginine (ADMA) in patients with early-onset coronary artery disease

BackgroundAsymmetric dimethylarginine (ADMA) has been associated with an increased risk of cardiovascular disease. We investigated the role of serum ADMA concentrations in early-onset coronary artery disease (EOCAD). MethodsCandidates for coronary artery angiography (age<50y for men and <55y for women) who met the inclusion criteria were enrolled in this study. Serum concentrations of ADMA were determined using ELISA. Severity of coronary atherosclerosis was estimated by number of diseased vessels. ResultsA total of 601 subjects (286 with EOCAD patients and 315 controls) were included in the study. ADMA concentrations were found to be significantly higher in the EOCAD group (0.480±0.110μmol/l) than in the control group (0.457±0.091, P=0.007). ADMA concentrations significantly increased with the number of diseased vessels (P<0.001). In addition, serum ADMA concentrations were affected by diabetes mellitus and smoking status, and were positively correlated with serum creatinine and body mass index (BMI). ConclusionsOur results show that serum ADMA concentrations were associated with the presence and severity of EOCAD, suggesting that ADMA may be involved in the progression of EOCAD.

L-Arginine Pathway Metabolites Predict Need for Intra-operative Shunt During Carotid Endarterectomy

Asymmetric dimethylarginine (ADMA) inhibits nitric oxide (NO) synthesis and is a marker of atherosclerosis. This study examined the correlation between pre-operative l-arginine and ADMA concentration during carotid endarterectomy (CEA), and jugular lactate indicating anaerobic cerebral metabolism, jugular S100B reflecting blood-brain barrier integrity, and with factors of surgical intervention. The concentration of l-arginine, ADMA, and symmetric dimethylarginine was measured in blood taken under regional anaesthesia from the radial artery of 55 patients prior to CEA. Blood gas parameters, concentration of lactate, and S100B were also serially measured in blood taken from both the radial artery and the jugular bulb before and after carotid clamping, and after release of the clamp. To estimate anaerobic metabolism, the jugulo-arterial ratio of CO2 gap/oxygen extraction was calculated. Positive correlation was found between pre-operative ADMA levels and the ratio of jugulo-arterial CO2 gap/oxygen extraction during clamp and reperfusion (p=.005 and p=.01, respectively). An inverse correlation was found between the pre-operative l-arginine concentration and jugular lactate at each time point (both p=.002). The critical pre-operative level of l-arginine was determined by receiver operator curve analysis. If l-arginine was below the cutoff value of 35μmol/L, jugular S100B concentration was higher 24h post-operatively (p=.03), and jugular lactate levels were increased during reperfusion (p=.02). The median pre-operative concentration of l-arginine was lower in patients requiring an intra-operative shunt than in patients without need of shunt (median: 30.3μmol/L [interquartile range 24.4-34.4μmol/L] vs. 57.6μmol/L [interquartile range 42.3-74.5μmol/L]; p=.002). High pre-operative ADMA concentration predicts poor cerebral perfusion indicated by elevated jugulo-arterial CO2 gap/oxygen extraction. Low pre-operative l-arginine concentration predicts the need for a shunt. The inverse correlation between pre-operative l-arginine concentration and both jugular lactate and S100B during carotid clamping suggests a protective role of the NO donor l-arginine.

Dimethylarginine Dimethylaminohydrolase 1 Protects Against High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice

High plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are associated with hepatic dysfunction in patients with nonalcoholic fatty liver disease (NAFLD). However, it is unknown whether ADMA is involved in the pathogenesis of NAFLD. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an enzyme that degrades ADMA. In this study, we used Ddah1-/- mice to investigate the effects of the ADMA/DDAH1 pathway on high-fat diet (HFD)-induced hepatic steatosis. After HFD feeding for 20 weeks, Ddah1-/- mice were more obese and had developed more severe hepatic steatosis and worse insulin resistance compared with wild-type (WT) mice. In the livers of HFD-fed mice, loss of DDAH1 resulted in higher levels of lipogenic genes, lower expression of β-oxidation genes, and greater induction of oxidative stress, endoplasmic reticulum stress, and inflammation than in the WT livers. Furthermore, ADMA treatment in HepG2 cells led to oxidative stress and steatosis, whereas overexpression of DDAH1 attenuated palmitic acid-induced steatosis, oxidative stress, and inflammation. Innovation and Conclusion: Our results provide the first direct evidence that the ADMA/DDAH1 pathway has a marked effect on hepatic lipogenesis and steatosis induced by HFD feeding. Our findings suggest that strategies to increase DDAH1 activity in hepatocytes may provide a novel approach to attenuate NAFLD development. Antioxid. Redox Signal. 26, 598-609.

Increased plasma asymmetric dimethylarginine is associated with cognitive deficits in patients with schizophrenia.

Cognitive deficits are a core feature of schizophrenia. Previous studies have shown that plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, was increased in patients with schizophrenia. This study aimed to investigate the association of ADMA with cognitive deficits in schizophrenia. Forty-seven patients with schizophrenia and 45 healthy control subjects were recruited in present study. Cognitive function was assessed with a neuropsychological battery including 7 neurocognitive tests. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale and plasma ADMA concentration was measured by HPLC. We found that patients with schizophrenia exhibited poorer performances in nearly all of the cognitive tests except for the visual memory index compared with healthy controls. Plasma ADMA levels were significantly increased in patients with schizophrenia when compared to normal controls, and the mean ADMA concentration in patients with multiple episode schizophrenia was much higher than that of patients with first episode schizophrenia. For the patients, ADMA was negatively associated with attention, working memory and executive function in schizophrenia. These results suggest that ADMA may be involved in the pathophysiology of schizophrenia-associated cognitive impairments, and plasma ADMA could be a peripheral biomarker for evaluation of cognitive function in schizophrenia.

Short-term esmolol attenuates remodeling of the thoracic aorta in hypertensive rats by decreasing concentrations of ADMA down-regulated by oxidative stress

Esmolol produces early regression of left ventricular hypertrophy and improves coronary artery remodeling, although the impact of short-term treatment with this beta-blocker on remodeling in large arteries has not yet been studied. We hypothesized that even a short (48h) course of esmolol might alter remodeling of the aorta in the spontaneously hypertensive rat (SHR). Fourteen-month-old male SHRs were treated intravenously with vehicle (SHR, n=8) or esmolol (SHR-E, n=8) (300μg/kg/min). Age-matched, vehicle-treated male Wistar-Kyoto rats (WKY, n=8) served as controls. After 48h, we studied the structure, volume density of elastic fibers, and passive mechanical properties of the aorta. Determination of asymmetrical dimethylarginine concentrations and total protein carbonyls in the aorta were analyzed. Esmolol significantly attenuated abnormal aortic wall thickness, cross-sectional area, wall-to-lumen ratio, volume density of elastic fibers, and wall stiffness. The protective effect of esmolol could be related to a decrease in asymmetrical dimethylarginine levels after down-regulation by oxidative stress. These findings could play a key role in the selection of antihypertensive therapy in patients with hypertension and aortic remodeling.

Dimethylarginine Dimethylaminohydrolase 2 (DDAH 2) Gene Polymorphism, Asymmetric Dimethylarginine (ADMA) Concentrations, and Risk of Coronary Artery Disease: A Case-Control Study.

Asymmetric dimethylarginine (ADMA) has been shown to be an independent predictor of cardiovascular diseases. Dimethylarginine dimethylaminohydrolase 2 (DDAH 2) promotes the metabolism of ADMA and plays a key role in the regulation of acute inflammatory response. With the present study, we investigated the relationship between DDAH 2 polymorphisms and risk of coronary artery disease (CAD) and its association to plasma ADMA concentrations. We used the haplotype-tagging SNP approach to identify tag SNPs in DDAH 2. The SNPs were genotyped by PCR and sequenced in 385 CAD patients and 353 healthy controls. Plasma concentrations of ADMA were determined using enzyme-linked immunosorbent assay (ELISA). A promoter polymorphism −449C/G (rs805305) in DDAH 2 was identified. Compared with the ADMA concentrations in CC genotype (0.328 ± 0.077 μmol/l), ADMA concentrations in CG + GG genotype were significantly increased (0.517 ± 0.090 μmol/l, P < 0.001). No significant associations between the −449C/G and risk of CAD were detected in the genetic models. The results of this study suggest that Genetic −499C/G polymorphism in DDAH 2 gene may affect the plasma ADMA concentrations in patients with CAD. However, it does not indicate a novel genetic risk marker for CAD.

Asymmetric dimethylarginine and arterial stiffness in patients with rheumatoid arthritis: A case-control study.

ObjectiveTo investigate whether levels of asymmetric dimethylarginine (ADMA), as a measure of endothelial dysfunction, are higher in patients with rheumatoid arthritis compared with healthy control subjects. The relationships between ADMA and surrogate measures of arterial stiffness were evaluated.MethodsPatients with rheumatoid arthritis and healthy control subjects were recruited. ADMA was quantified via enzyme-linked immunosorbent assay. Arterial stiffness was evaluated using pulse wave analysis.ResultsThere was no significant difference in plasma ADMA concentration between patients with rheumatoid arthritis (n = 30) and healthy controls (n = 30). Aortic augmentation pressure was significantly higher in patients than in controls. C-reactive protein and Health Assessment Questionnaire score were independent predictors of arterial stiffness in patients. There was no relationship between ADMA concentration and aortic augmentation pressure in the study population as a whole.ConclusionsArterial stiffness appears to be increased in rheumatoid arthritis and independently associated with systemic inflammation and physical disability. ADMA concentration was not increased in this small group of patients with rheumatoid arthritis compared with healthy controls; nor was it associated with arterial stiffness.

Risk factors for chronic kidney disease do not influence the serum levels of asymmetric dimethylarginine in HIV-1-infected patients without significant renal disease.

INTRODUCTION Chronic kidney disease (CKD) is one of the consequences of human immunodeficiencyvirus-1 (HIV-1) infection. The disease increases the risk of progression to acquired immunodeficiencysyndrome and death and complicates antiretroviral therapy. The prevalence of CKD in HIV-1-infectedpatients is difficult to estimate and depends on the diagnostic criteria for CKD. OBJECTIVES The aim of the study was to evaluate the usefulness of a single measurement of serum asymmetricdimethylarginine (ADMA) levels in the diagnosis of kidney damage in patients infected with HIV-1. PATIENTS AND METHODS The study included 119 HIV-1-infected individuals (88 males [74%]), both onantiretroviral treatment and treatment-naive, with a negative history of kidney disease, and 31 healthyvolunteers. We analyzed demographic characteristics as well as data on concomitant diseases, antiretroviralregimen, serum ADMA concentrations, parameters of renal function, CD4+ cell count, and HIV-1viral load. RESULTS No significant impairment of renal function was observed. Mean serum ADMA levels in allHIV-1-infected patients, as well as in treatment-naive patients and treated patients, were significantlyhigher (P <0.0001; P = 0.0001; P <0.0001; respectively) compared with those in the control group.The difference between treatment-naive and treated HIV-1-infected patients was nonsignificant. ADMAlevels were not correlated with the mean duration of antiretroviral therapy, antiretroviral drugs used, orother risk factors for CKD. CONCLUSIONS A single measurement of ADMA levels is not useful for the diagnosis of CKD in patients withoutsignificant renal pathology or as an indicator of kidney damage related to antiretroviral therapy. The significanceof repeated measurements of ADMA levels in renal function assessment requires further research.

Plasma asymmetric dimethylarginine (ADMA) levels in Mexican women exposed to polycyclic aromatic hydrocarbons (PAHs): A preliminary study

Recent studies indicate that exposure to environmental pollutants (as polycyclic aromatic hydrocarbons) is a very important risk factor for development of cardiovascular diseases (CVDs). Correspondingly, in recent times asymmetric dimethylarginine (ADMA) has been proposed as a new and meaningful biomarker predictor for the risk of CVDs. Therefore, the objective of this study was to evaluate plasma ADMA concentrations in Mexican women (n=155) exposed to polycyclic aromatic hydrocarbons (PAHs). Urinary 1-hydroxypyrene [(1-OHP), exposure biomarker for PAHs] levels were quantified using a high performance liquid chromatography (HPLC) technique and plasma ADMA concentrations were analyzed using a commercially available ELISA kit. Urinary 1-OHP levels in all women assessed ranged from <LOD to 8.80μmol/mol creatinine. Regarding plasma ADMA concentrations, the mean levels ranged from 0.66 to 1.00μmol/L. Moreover, a significantly relationship was found between plasma ADMA concentrations and urinary 1-OHP levels (p=0.005; r=0.390). In conclusion, the results showed in this study demonstrated that the urinary 1-OHP levels were significant predictors of plasma ADMA concentrations in Mexican women exposed to PAHs. Although with due caution regarding the low representativeness of the present screening, it can be considered as a preliminary work to perform prospective studies including greater number of individuals and focusing in a more complete characterization of the effects produced by PAHs exposure on cardiovascular health.