Serum Asymmetric Dimethylarginine Research Articles

Value of Serum Asymmetric Dimethylarginine (ADMA) As a Novel Biomarker for Uveitis in Behçet’s Disease

ABSTRACT Purpose To evaluate the serum asymmetric dimethylarginine (ADMA) level as a biomarker for uveitis in Behçet’s Disease (BD). Methods In this cross-sectional study, two groups of BD patients were examined: 33 with uveitis and 27 without uveitis. All patients were clinically evaluated, with disease activity measured by Behçet’s Disease Current Activity Form (BDCAF) score. They also underwent thorough ophthalmic evaluation, and routine laboratory investigations, including serum ADMA. Results Patients with BD who experienced active or inactive uveitis had higher levels of serum ADMA compared to those without uveitis. Anterior (ρ = 0.34, p < 0.01), posterior (ρ = 0.3, p < 0.05), and pan uveitis (ρ = 0.35, p < 0.01) were significantly correlated with serum ADMA levels. However, there was no significant correlation between ADMA and other BD manifestations. ROC curve analysis showed that increased serum ADMA levels in BD patients predicted uveitis with a sensitivity of 61.8%, specificity of 96.2%, and AUC of 0.78(95% CI: 0.66–0.9, p < 0.001). Conclusion Serum ADMA level can serve as a novel biomarker of uveitis in BD and its severity with good diagnostic accuracy, regardless of its site or activity.

Serum endocan, asymmetric dimethylarginine and lipid profile in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a chronic inflammatory disease, and it is thought that subclinical inflammation persists even when there are no attacks, eventually causing endothelial dysfunction (ED) and atherosclerosis. Limited data are available about serum endocan, asymmetric dimethylarginine (ADMA) and lipid profile in children with FMF, so we aimed to evaluate these markers in children with FMF during the attack-free period. A total of 50 patients diagnosed with FMF and 50 age and sex-matched healthy children were recruited. Serum endocan, ADMA and lipid profiles were measured. Also, atherogenic indices (Castelli's risk indices I and II [CRI I and II], atherogenic index of plasma [AIP] and atherogenic coefficient [AC]) were calculated. Serum endocan, ADMA levels, low-density lipoprotein cholesterol, triglycerides, CRI II and AIP of the FMF patients were significantly higher than controls (p < 0.001). Unlike serum endocan, serum ADMA showed a positive significant correlation with total cholesterol, non-high density lipoprotein cholesterol, CRI I, AIP and AC (p < 0.001, p < 0.001, p = 0.004, p = 0.028, p = 0.004 respectively). Serum ADMA and lipid profile might be used as potential markers for endothelial dysfunction and increased cardiovascular risk in FMF patients. Theoretically, serum ADMA may affect lipid profiles and serum endocan represents an intriguing biomarker related to inflammation. Coexistence of dyslipidemia represents an additional risk factor that contributes to the onset of early atherosclerosis. A few studies investigated the role of changes in lipid profile and lipid ratios in accelerated atherosclerosis pathogenesis in FMF patients. The relationship between colchicine and lipid profile is contradictory. Although colchicine can cause dyslipidemia, it also has anti-atherosclerosis effects. Elevated ADMA level and atherogenic indices in FMF children reflect their potential role in the early detection of cardiovascular affection in FMF patients.

Evaluation of Asymmetric Dimethylarginine, Malondialdehyde, and Vitamin Levels of Borderline Personality Disorder Patients With and Without Self-Mutilation.

Believing that oxidative stress may be increased in borderline personality disorder (BPD) patients with self-mutilating behaviors (SMB), we aimed to measure serum asymmetric dimethylarginine (ADMA) and malondialdehyde (MDA) levels in these patients. The study included 60 patients diagnosed with BPD and 30 healthy controls. BPD patients were divided into two groups: 30 female patients with SMB and 30 female patients with no-self-mutilating behavior (NSMB). ADMA, MDA, vitamin A, and vitamin E levels were analyzed. Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were conducted with the participants. Serum ADMA and MDA levels were higher in SMB and NSMB group compared to control group. Serum vitamin E levels were also lower in the SMB group compared to the control group. Positive correlations were determined between both ADMA and MDA, and between BDI and BAI scores. Also, BAI scores were statistically higher in SMB group compared to NSMB group. It was discovered that levels of ADMA and MDA, which reflected oxidative stress, were elevated in patients with BPD who exhibited SMB. Accordingly, future studies should investigate the role of oxidative stress in a more comprehensive way in terms of the different mechanisms underlying and treatments involved in borderline personality disorder.

Relationships between polymorphisms in keratin genes and Alzheimer’s disease phenotypes.

AbstractBackgroundKeratins are genetically polymorphic and are the largest subset of intermediate filaments. Keratins are also implicated in signaling pathways, inflammation, and disease states. Keratin 9 (KRT9) protein has been identified to have high diagnostic accuracy for Alzheimer’s disease (AD) (PMID:22045497); it was detected in cerebrospinal fluid (CSF) of AD patients but not healthy controls (PMID:24959311). Plasma keratin 9 concentrations also positively correlated with AD‐associated proteins (e.g., apolipoprotein E and tau) in AD patients (PMID:26973255). Post‐translational modification of keratin 83 (KRT83) protein has been associated with serum asymmetric dimethylarginine levels (PMID:34181092), a vascular risk factor implicated in AD. However, our understanding of the role of genetic variation in AD risk is incomplete. Here, we investigate associations between single nucleotide polymorphisms (SNPs) in KRT9, KRT83, and KRT2 (Keratin 2, couples with keratin 9) and AD biomarker phenotypes.MethodIndividuals with mild cognitive impairment (MCI) or AD, and clinically normal controls were selected among ADNI participants. Participants underwent genome‐wide genotyping. Keratin gene variants were identified from the genome‐wide data using dbSNP variant IDs and genotypes were coded additively. Linkage‐disequilibrium‐based clumping on minor allele frequency (MAF) was applied to prioritize more common SNPs. CSF‐Aβ42, ‐tau, and phosphorylated‐tau (p‐tau) levels were quantified via Roche Elecsys immunoassays. Brain‐Aβ deposition was evaluated via normalized PET‐18F‐AV‐45 cortical summary measures (SUVR). White matter hyperintensities (WMH) were obtained from MRI 3D‐T1 and FLAIR sequences via an automated atlas‐based segmentation pipeline. Linear regression models controlling for age, sex, Mini‐Mental State Exam, APOE‐ε4 status, and head size were used to assess association and interaction effects between SNPs and the AD phenotypes in R.ResultAmong included participants (n = 907, 73±7.2 years, 44% female), SNPs in KRT2 (e.g. 3’UTR‐variant rs117041267‐G/A; MAF = 1.4%) and KRT83 (e.g. upstream‐variant KRT83‐rs17119838‐C/T; MAF = 15.6%) were associated with higher CSF‐Aβ42 concentrations (F(2,905) = 4.26,p = 0.014; and F(2,905) = 6.61,p = 0.0014, respectively). Upstream‐variant KRT83‐rs182354391‐C/G (MAF = 1%) showed an association with lower CSF‐tau (F(1,904) = 5.44,p = 0.020). Multiple KRT9 and KRT2 SNPs also showed association with WMH, while KRT2 and KRT83 intron variants showed associations with PET‐Aβ.ConclusionThese candidate gene analyses suggest involvement of multiple keratin family genes in AD, as indicated by differences in amyloid and tau biomarkers, and white matter disease.

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.&#x0D; 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.&#x0D; 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).&#x0D; The following parameters were measured: ADMA, symmetrical dimethylarginine (SDMA), N-monomethyl-L-arginine (NMMA), and total nitric oxide.&#x0D; 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).&#x0D; 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.

DDAH1 Protects against Cardiotoxin-Induced Muscle Injury and Regeneration.

Nitric oxide (NO) is an important biological signaling molecule affecting muscle regeneration. The activity of NO synthase (NOS) is regulated by dimethylarginine dimethylaminohydrolase 1 (DDAH1) through degradation of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA). To investigate the role of DDAH1 in muscle injury and regeneration, muscle-specific Ddah1-knockout mice (Ddah1MKO) and their littermates (Ddah1f/f) were used to examine the progress of cardiotoxin (CTX)-induced muscle injury and subsequent muscle regeneration. After CTX injection, Ddah1MKO mice developed more severe muscle injury than Ddah1f/f mice. Muscle regeneration was also delayed in Ddah1MKO mice on Day 5 after CTX injection. These phenomena were associated with higher serum ADMA and LDH levels as well as a great induction of inflammatory response, oxidative stress and cell apoptosis in the gastrocnemius (GA) muscle of Ddah1MKO mice. In the GA muscle of CTX-treated mice, Ddah1 deficiency decreased the protein expression of M-cadherin, myogenin, Bcl-2, peroxiredoxin 3 (PRDX3) and PRDX5, and increased the protein expression of MyoD, TNFα, Il-6, iNOS and Bax. In summary, our data suggest that DDAH1 exerts a protective role in muscle injury and regeneration.

Preeklamptik Anne ve Bebeklerinde Asimetrik Dimetil Arjinin ve Oksidan/Antioksidan Düzeyi

Aim: It is thought that asymmetric dimethyl arginine(ADMA) level is significantly higher in pregnant&#x0D; women with preeclampsia compared to healthy pregnant women, ADMA elevation develops before&#x0D; the clinical signs of preeclampsia, and ADMA plays a role in the pathogenesis of preeclampsia. In this&#x0D; study, it was aimed to investigate whether serum ADMA, total nitrite and nitrate (NOx), arginine and&#x0D; total antioxidant capacity (TAC) and levels in placenta samples taken from healthy and preeclamptic&#x0D; pregnant women and their babies are associated with preeclampsia, whether preeclampsia can be&#x0D; detected beforehand with these markers, and whether possible problems that may develop in the&#x0D; mother and baby can be prevented as a result.&#x0D; Material and Methods: 62 pregnant women and their babies who were followed up in Zonguldak&#x0D; Bülent Ecevit University obstetrics service are divided two groups; 31 preeclamptic pregnant and babies&#x0D; (Group I), formed Patient group; 31 pregnant and babies without preeclampsia (Group II), formed&#x0D; Control Group. Blood samples were obtained from mothers before birth, from the cord during birth, from&#x0D; babies in first 24 hours after birth and placenta samples were obtained from each pregnant to evaluate&#x0D; in the study. Age, weight, initial pregnancy state, pregnancy period, systolic and diastolic blood pressure&#x0D; levels of mothers with and without pre-eclampsia diagnosis, while birth weights, genders, problems and&#x0D; complications during treatment process, clinic and laboratory properties, prognosis, ADMA, arginine,&#x0D; NOx and TAC levels of babies were examined in this study.&#x0D; Results: There was no significant difference between two groups about antenatal factors that effect&#x0D; on prognosis. In the comparison of blood values, ADMA level of preeclamptic group was significantly&#x0D; higher (p

Cardiovascular evaluation and endothelial dysfunction in Cushing syndrome following remission: a prospective study.

Cushing syndrome (CS) is a well-known risk factor for cardiovascular morbidities. We aimed to evaluate endothelial and cardiovascular functions, endothelial mediators and pro-inflammatory cytokines in patients with CS before and after remission. Adult patients with newly diagnosed endogenous CS were included. Metabolic [body mass index (BMI), glucose, and lipid values] and cardiovascular evaluation studies [24-h ambulatory blood pressure monitoring, carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and echocardiography] were performed, and endothelial mediators [asymmetric dimethyl arginine (ADMA) and endothelin-1 (ET-1)] and pro-inflammatory cytokines [interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α)] were measured. Control group was matched in terms of age, gender, and BMIs. Twenty-five patients, mean age 40.60 ± 14.04years, completed the study. Compared to controls (n = 20) mean arterial pressure (MAP) and CIMT were higher (p < 0.005 and p = 0.012, respectively), and FMD (p < 0.001) and mitral E/A ratio (p = 0.007) lower in the patients during active disease. Baseline serum ADMA, ET-1, and IL-1β were similar between the groups, while TNF-α was lower in the patients (p = 0.030). All patients were in complete remission 1 year following surgery. BMI, LDL cholesterol, serum total cholesterol, fasting plasma glucose, MAPs, and CIMT significantly decreased (p < 0.005), while there was no improvement in FMD (p = 0.11) following remission. There was no significant change in ADMA, IL-1β, and TNF-α levels, but ET-1 increased (p = 0.011). Remission in CS improves some cardiovascular parameters. ADMA and ET-1 are not reliable markers for endothelial dysfunction in CS. Metabolic improvements may not directly reflect on serum concentrations of TNF-α and IL-1β following remission of CS.

Assessment of serum asymmetric dimethylarginine level in children with beta-thalassemia

Assessment of serum asymmetric dimethylarginine level in children with beta-thalassemia

Effects of febuxostat on markers of endothelial dysfunction and renal progression in patients with chronic kidney disease

Hyperuricemia relates to chronic kidney disease (CKD) progression and impaired endothelial function. Febuxostat is potent and effective for decreasing serum uric acid levels. Information for the effect of febuxostat treatment on markers of endothelial dysfunction and renal injury among patients with CKD remains limited. A total of 84 patients with CKD stages III-IV with asymptomatic hyperuricemia were randomly assigned to either the febuxostat (40 mg/day, N = 42) or the matching control (N = 42) group for 8 weeks. Serum asymmetric dimethylarginine (ADMA), estimated glomerular filtration rate (eGFR), urine albumin, high sensitivity C-reactive protein (hs-CRP), ankle brachial index (ABI) and serum uric acid were measured at baseline and at the end of study. Febuxostat administration significantly reduced the serum uric acid concentration among patients with CKD when compared with control [− 3.40 (95% CI − 4.19 to − 2.62) vs. − 0.35 (95% CI − 0.76 to 0.06) mg/dL; P < 0.001, respectively). No significant difference in the changes in serum ADMA, hs-CRP, eGFR and albuminuria was identified between the two groups. Subgroup analysis among patients with decreased serum uric acid after febuxostat, the estimated GFR change between the febuxostat and the control group showed significant difference at 8 weeks (2.01 (95% CI 0.31 to 3.7) vs. 0.04 (95% CI − 1.52 to 1.61) mL/min/1.73 m2; P = 0.030, respectively). Adverse events specific to febuxostat were not observed. Febuxostat effectively reduced serum uric acid in the CKD population without improving endothelial dysfunction. It was able to preserve renal function in the subgroup of patients with CKD and lower serum uric acid level after treatment.Trial registration: Thai Clinical Trials, TCTR20210224005: 24/022021 http://www.thaiclinicaltrials.org/show/TCTR20210224005.

Hepatic DDAH1 mitigates hepatic steatosis and insulin resistance in obese mice: Involvement of reduced S100A11 expression.

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is an important regulator of plasma asymmetric dimethylarginine (ADMA) levels, which are associated with insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). To elucidate the role of hepatic DDAH1 in the pathogenesis of NAFLD, we used hepatocyte-specific Ddah1-knockout mice (Ddah1HKO) to examine the progress of high-fat diet (HFD)-induced NAFLD. Compared to diet-matched flox/flox littermates (Ddah1f/f), Ddah1HKO mice exhibited higher serum ADMA levels. After HFD feeding for 16 weeks, Ddah1HKO mice developed more severe liver steatosis and worse insulin resistance than Ddah1f/f mice. On the contrary, overexpression of DDAH1 attenuated the NAFLD-like phenotype in HFD-fed mice and ob/ob mice. RNA-seq analysis showed that DDAH1 affects NF-κB signaling, lipid metabolic processes, and immune system processes in fatty livers. Furthermore, DDAH1 reduces S100 calcium-binding protein A11 (S100A11) possibly via NF-κB, JNK and oxidative stress-dependent manner in fatty livers. Knockdown of hepatic S100a11 by an AAV8-shS100a11 vector alleviated hepatic steatosis and insulin resistance in HFD-fed Ddah1HKO mice. In summary, our results suggested that the liver DDAH1/S100A11 axis has a marked effect on liver lipid metabolism in obese mice. Strategies to increase liver DDAH1 activity or decrease S100A11 expression could be a valuable approach for NAFLD therapy.

Efficacy of beetroot juice on reducing blood pressure in hypertensive adults with autosomal dominant polycystic kidney disease (BEET-PKD): study protocol for a double-blind, randomised, placebo-controlled trial

BackgroundIn autosomal dominant polycystic kidney disease (ADPKD) impaired nitric oxide (NO) synthesis, in part, contributes to early-onset hypertension. Beetroot juice (BRJ) reduces blood pressure (BP) by increasing NO-mediated vasodilation. The aim of this double-blind, randomised, placebo-controlled study is to test the hypothesis that BRJ reduces systolic and diastolic clinic BP in hypertensive adults with ADPKD.MethodsParticipants with ADPKD and treated hypertension (n = 60) will be randomly allocated (1:1) to receive a daily dose of either nitrate-replete (400 mg nitrate/day) or nitrate-deplete BRJ for 4 weeks. The co-primary outcomes are change in mean systolic and diastolic clinic BP before and after 4 weeks of treatment with daily BRJ. Secondary outcomes are changes in daily home BP, urinary albumin to creatinine ratio, serum and salivary nitrate/nitrite levels and serum asymmetric dimethylarginine levels before and after 4 weeks of BRJ.DiscussionThe effect of BRJ in ADPKD has not been previously tested. BRJ is an accessible, natural dietary supplement that, if effective, will provide a novel adjunctive approach for treating hypertension in ADPKD.Trial registrationClinicalTrials.gov NCT05401409. Retrospectively registered on 27th May 2022.

Effect of serum adropin levels on circulating endothelial dysfunction biomarkers in COVID-19 patients

Purpose: Several studies show that the symptoms of severe COVID-19 infection reflect the clinical phenotype of endothelial dysfunction and share common pathophysiological mechanisms with endothelial dysfunction. Therefore, the aim of the study was to investigate the effect of serum adropin levels on endothelial dysfunction biomarkers and determine whether adropin could be a new biomarker for COVID-19.&#x0D; Materials and Methods: The study included 40 patients with mild/moderate COVID-19, 48 patients with severe/critical COVID-19, and 37 controls. Serum adropin and circulating biomarkers of endothelial dysfunction including asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble intercellular adhesion molecule-1 (sICAM-1) and plasminogen activator inhibitor-1 (PAI-1) levels were determined by micro-ELISA.&#x0D; Results: Serum adropin levels were found to be significantly higher in COVID-19 patients (165.2±11.49 pg/ml) than in controls (85.46±12.08 pg/ml). Serum adropin levels of patients with severe/critical symptoms (194±16.23 pg/ml) were significantly higher than the patients with mild/moderate symptoms (130.6 ±14.53). In addition, serum ADMA, eNOS, and, ET-1 levels were significantly higher in the COVID-19 subjects (150.5±8.67 ng/ml, 172.4±14.01 pg/ml, 159.3±10.19 pg/ml, respectively) than that those in the controls (104.5±9.182 ng/ml, 141.4±17.74 pg/ml, 100.1±11.37 pg/ml, respectively). Significant positive correlations were found between adropin and ADMA, eNOS, ET-1, sICAM-1, and PAI-1 levels in the patients.&#x0D; Conclusion: We suggest that adropin may be a new potential biomarker for COVID-19 and an important molecule in restoring endothelial cell damage. Positive correlations between serum adropin levels and ADMA, eNOS, ET-1, sICAM-1 and PAI-1 levels in patients suggest that adropin may compensate for damage to endothelial cells.

Endometrioziste oksidatif stres ve apoptozla ilişkili biyobelirteçlerin düzeyleri

Purpose: In this study, the apoptosis marker M30, the oxidative stress markers malondialdehyde, (MDA) and asymmetric dimethyl arginine (ADMA) have been studied in the context of endometriosis.&#x0D; Materials and Methods: This prospective case-control study comprises 31 patients diagnosed with endometriosis and 31 controls. ADMA and M30 levels in blood serum were measured by the enzyme-linked immunosorbent assay (ELISA) method, and MDA levels were measured by the spectrophotometric method. In addition, some biochemical parameters and cancer antigen-125 (CA-125) levels were also measured.&#x0D; Results: M30 levels were statistically lower in endometriosis patients (271.5 IU/L) than in controls (371.3 IU/L). ADMA levels were higher in endometriosis patients (19.3 ng/L) compared to controls (12.7 ng/L). CA-125 levels were statistically higher in the endometriosis patients (65.1 U/mL) compared to the controls (19.0 U/mL). There was no significant difference between the two groups in MDA levels. The results regarding dyspareunia, pelvic pain, AST, and ALP were statistically significant.&#x0D; Conclusion: In our study, decreased M30 levels in the patient group were associated with reduced apoptosis in endometriosis. ADMA levels, elevated with the increase of oxidative stress, were higher in the patients. MDA levels, an indicator of increased oxidative stress, were also higher in the patient group. This study constitutes the first data regarding endometriosis patients' ADMA, M30, and MDA levels.

Validation of Serum ADMA Levels as a Biomarker for Assessing Cardiovascular Risk in Patients with Coronary Heart Disease: A Study from a Tertiary Care Hospital in Pakistan

Objectives: The diagnostic potential of serum asymmetric dimethylarginine (ADMA) levels as a biomarker for cardiovascular risk has been investigated in various populations, but no such study has been reported in Pakistan. This study aimed to assess the diagnostic efficiency of serum ADMA levels in detecting cardiovascular risk in patients with coronary heart disease (CHD). Methodology: A cross-sectional study was conducted at the Chaudhry Pervaiz Elahi Institute of Cardiology (CPEIC), Wazirabad, Pakistan, using a consecutive sampling technique to ensure randomization. One hundred individuals were divided into two groups (CHD patients and healthy controls), and blood samples were collected between January 2022 and November 2022. Serum ADMA levels were measured using an enzyme-linked immunosorbent assay (ELISA), and statistical analysis was performed to determine the area under the receiver operating characteristic (ROC) curve (AUC). Results: The mean age of CHD patients' serum samples was 58.6 ± 7.39 years (p&lt;0.001) compared to 42.26 ± 14.4 years (p&lt;0.001) in healthy controls. The mean ADMA concentration in the serum of CHD patients was determined as 1.37 ± 0.26 µmol/L (p&lt;0.001) compared to 0.812 ± 0.207 µmol/L (p&lt;0.001) in healthy controls. The AUC on the ROC curve was determined as 0.95, indicating high diagnostic accuracy. ADMA's sensitivity, specificity, and overall accuracy were determined as 82%, 88%, and 85%, respectively. Conclusion: In conclusion, serum ADMA levels demonstrate a promising potential as a biomarker for assessing cardiovascular risk. The findings of this study suggest that ADMA measurements could be utilized as a diagnostic tool in CHD patients, aiding in the identification and management of cardiovascular risk in the Pakistani population. Further research is warranted to validate these findings and explore the utility of ADMA in more extensive and diverse cohorts.

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.

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

Background: 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). Methods: Methods: 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. Results and Conclusion: 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.

Circadian blood pressure variability and asymmetric dimethylarginine in patients with glaucoma: cross-sectional study of The LIGHT cohort.

Glaucoma is reportedly associated with asymmetric dimethylarginine (ADMA) and circadian blood pressure (BP) variability, including night-time SBP. We determined whether ADMA level is associated with night-time SBP in patients with glaucoma. In this cross-sectional study, we measured the serum ADMA level and ambulatory BP of 163 patients with glaucoma and 705 participants without glaucoma. Based on the tertiles of serum ADMA level, the patients were divided into three groups: low, intermediate, and high-ADMA. Night-time SBP was determined based on ambulatory BP measured every 30 min for 48 h. The nondipper BP pattern was defined as having a night-time mean SBP decline of less than 10% relative to the mean daytime SBP. In the glaucoma group, the night-time SBP in the high-ADMA group was significantly higher than in the low-ADMA group (123.0 and 114.4 mmHg, respectively; P = 0.003). Multivariable analysis adjusted for the potential confounders showed the night-time SBP, and the odds ratio for nondipper in the high-ADMA group were also significantly higher than in the low-ADMA group ( P = 0.030 and P = 0.021, respectively). Significant associations between continuous serum ADMA levels with night-time SBP and nondipper were also found ( P = 0.002 and 0.006, respectively). In the control group, however, no significant associations were found between serum ADMA levels and night-time SBP and nondipper. A significant interaction effect of the serum ADMA levels and glaucoma on nondipper was found ( P = 0.004). Serum ADMA level was significantly associated with the disturbance of circadian BP variability in patients with glaucoma.

Effect of cigarette smoking on serum methylarginine and α-klotho levels

Background and aimsSmoking causes many diseases such as cardiovascular, lung diseases, stroke and premature aging. However, the role of smoking in the pathogenesis of these diseases is unclear. Increasing evidence suggests that methylarginine pathway metabolites and α-klotho may be strong markers for pathologies such as premature aging, endothelial dysfunction, and oxidant damage. Therefore, the study aimed to measure the serum levels of arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), N-monomethyl-l-arginine (L-NMMA), and α-klotho levels in smokers. Methods and resultsThis case-control analytical study included 65 smokers and 71 non-smokers. Sociodemographic characteristics, routine biochemistry parameters, Framingham risk scores and Fagerström Nicotine Dependence Test (FTND) were recorded. Serum methylarginine and α-klotho levels were analyzed by tandem mass spectrometry and enzyme-linked immunosorbent assay (ELISA), respectively. Serum ADMA (p < 0.001), L-NMMA (p = 0.024), SDMA (p < 0.001) levels of smokers were higher than non-smokers, and serum α-klotho (p < 0.001) and arginine levels (p < 0.001) were lower. There was a positive correlation between serum ADMA levels with FNDT, age and pack/year in smokers, while there was a negative correlation between klotho levels and age. A positive correlation was found between serum ADMA levels, Framingham risk score and age in non-smokers. ConclusionSmoking is related to premature aging and is a strong risk factor for various diseases such as cardiovascular, inflammatory, and renal diseases. Elevated serum methylarginine and decreased serum klotho levels were found in smokers. Therefore, our findings suggest that smoking may be involved in the pathogenesis of these diseases by affecting α-klotho and methylarginine-related pathways.

The effects of proton pump inhibitors on the development of post-stenting major adverse cardiovascular events in patients with acute coronary syndrome

Proton pump inhibitors (PPIs) are recommended for the prevention of gastrointestinal bleeding in acute coronary syndrome (ACS) patients who receive dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) but have been associated with an increased risk of major adverse cardiovascular events (MACE) in these patients. We aimed to investigate the relationship between serum asymmetric dimethylarginine (ADMA) and copeptin levels and MACE in those who started on imminent DAPT and PPI therapy after PCI. 90 patients with ACS were included in this prospective observational study and divided into three groups lansoprazole (n=30), rabeprazole (n=31), and pantoprazole (n=29). The serum ADMA and copeptin levels were examined at the time of diagnosis, at the end of 1st and 6th month. MACE was defined as mortality, recurrent AMI (acute myocardial infarction), and CST (coronary stent thrombosis) development after PCI. MACE developed in two patients in the first month and eight patients (8.9%) after six months of follow-up. At six months, CST was seen in only two patients (2.2%). At the first-month evaluation, while a significant increase was observed in serum ADMA levels at the time of admission (p&lt;0.001), the copeptin levels decreased significantly in all patients (p&lt;0.001). In the 6th month, the serum ADMA and copeptin levels significantly increased compared to the time of admission and 1st-month evaluation in all groups (p&lt;0.001). PPIs might significantly influence serum ADMA and copeptin levels in patients undergoing coronary stenting due to ACS. Nevertheless, we did not notice clinical extrapolation of the potential effects.