Serum Asymmetric Dimethylarginine Levels Research Articles

Association of Serum Asymmetric Dimethylarginine with the Severity of Coronary Artery Disease: A Pilot Study.

Asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase (NOS), has been implicated in endothelial dysfunction and atherogenesis. Though there is much evidence linking ADMA with atherosclerosis and adverse cardiovascular events, only a few studies have established the independent relationship between elevated ADMA and the angiographic extent of coronary artery disease (CAD). The aim of the study was to analyze serum ADMA levels in patients with varied extent and severity of coronary atherosclerosis and to see whether the levels of ADMA in male and female participants vary significantly. We analyzed 40 individuals with obstructive CAD, including men and women, between the ages of 30 and 60. According to their coronary angiographic reports, the participants were divided into four groups: minor CAD, single vessel disease (SVD), double vessel disease (DVD) group and triple vessel disease (TVD). Then, serum ADMA levels was measured and compared among these groups. ADMA level was significantly higher in patients with TVD (167.74±16.69) than those in the DVD (159.46±10.40), SVD (149.54±16.39) and minor CAD (144.5± 24.16) group (p-value= 0.0001). There was no significant difference in ADMA levels between male and female participants (p= 0.534). ADMA concentration in the serum may be useful in identifying whether CAD correlates significantly to the extent and severity of coronary atherosclerosis.

α-Klotho, Plasma Asymmetric Dimethylarginine, and Kidney Disease Progression

Rationale & ObjectiveWe aimed to explore the associated factors of endothelial injury in chronic kidney disease (CKD) and the relationship between endothelial dysfunction and CKD prognosis.Study DesignA prospective observational cohort study.Setting & Participants77 adults with CKD stages 1-5 were enrolled January 2010 to December 2010 and followed up until December 2015.ExposureSerum asymmetric dimethylarginine (ADMA) level at baseline, α-klotho, sodium-phosphorus synergistic transporter, and dimethylarginine-dimethylamine hydrolase expression in kidney biopsy samples.OutcomeInitiation of kidney replacement therapy (KRT).Analytical ApproachKaplan-Meier analysis was used for evaluation of the incidence rate of KRT. All tests were 2 tailed, and statistical significance was defined as P < 0.05.ResultsMean serum ADMA level of 77 patients was 64.3 ± 34.6 ng/mL. ADMA level increased with CKD stages (P = 0.06) and declining kidney function (r = −0.267; P = 0.02). The expression of α-klotho in kidney biopsy specimens also decreased. Median follow-up time was 56 (interquartile range, 50.5-62) months. Kaplan-Meier analyses showed that during a total follow-up of 6 years, the incidence of KRT initiation in the high-ADMA group was significantly higher than that in the low group (35.9% vs 13.2%; P = 0.03). ADMA level was negatively correlated with α-klotho (r = −0.233; P = 0.04) and positively correlated with phosphorus level (r = 0.243; P = 0.04). The expression of sodium-phosphorus synergistic transporter in kidney tubules, which promoted phosphorus reabsorption, and the expression of dimethylarginine-dimethylamine hydrolase isoform 1, which regulated ADMA, were decreased. Correlation analysis also showed that ADMA level decreased while age increased at baseline (r = −0.292; P = 0.01).LimitationsSmall sample size with limited longer-term follow-up.ConclusionsSerum ADMA levels increased as kidney function declined, and high serum ADMA level was associated with incident kidney failure. Low tissue α-klotho and high levels of plasma phosphorus or tissue expression of type II sodium/phosphate cotransporter in the kidney are associated with higher circulating ADMA levels, suggesting that they may be involved in the pathogenesis of endothelial dysfunction in patients with CKD.

The Serum Levels of Asymmetric Dimethylarginine, Vascular Endothelial Growth Factor, and Insulin-Like Growth Factor-1 in Preterms with Retinopathy of Prematurity

Objective: To determine the serum levels of asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) in preterms with retinopathy of prematurity (ROP). Materials and Methods: We included 37 preterm infants. The first blood samples were obtained within the first 5 days of life and repeated at the time of the first ophthalmologic examination for ROP. The levels of ADMA, IGF-1, and VEGF were measured in all samples. Results: ROP was detected in 12 of the subjects (32.4%). We categorized the subjects as non-ROP (Group 1; n = 25), untreated ROP (Group 2; n = 7), and treated ROP (Group 3; n = 5) according to the eye findings. There were no significant differences among the groups for serum levels of ADMA, VEGF, and IGF-1 at the first sampling. Conclusion: We did not find any differences in terms of serum ADMA, IGF-1, and VEGF levels in preterm infants with or without ROP.

Evaluation of Asymmetric Dimethylarginine Levels in Patients With Chronic Thromboembolic Pulmonary Hypertension Undergoing Pulmonary Endarterectomy

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary embolism, and pulmonary endarterectomy (PEA) is the surgical treatment. Asymmetric dimethylarginine (ADMA) levels are increased in pulmonary hypertension. This study aimed to investigate serum ADMA levels in patients with CTEPH, the effect of PEA on ADMA, and its prognostic value in long-term mortality. Eighty (80) patients with CTEPH and 32 healthy controls were included. Preoperative serum ADMA levels, determined using an enzyme-linked immunosorbent assay, were compared between patients with CTEPH and controls. Of 80 patients, 64 had PEA. Pre- and 6-month postoperative serum ADMA levels, 6-minute walk distance (6MWD), and haemodynamic parameters were collected from patients undergoing PEA. Patients were followed-up for survival analysis. Mean ± standard deviation serum ADMA levels were significantly higher in patients with CTEPH compared with controls (0.79±0.32 μmol/L vs 0.52±0.12 μmol/L; p=0.0001). Statistically significant differences were observed between preoperative and postoperative serum ADMA levels (0.78±0.30 μmol/L vs 0.62±0.22 μmol/L; p=0.0001), 6MWD (p=0.0001), and pulmonary vascular resistance (p=0.0001) in 60 patients who underwent and survived PEA. The decrease in serum ADMA levels and increase in 6MWD were significantly correlated (r=-0.286, p=0.027). No other correlation was found. Perioperative mortality was 6.3%, and the survival rate with a mean follow-up of 34.57±8.20 months was 93.3%. Patients with serum ADMA levels >0.8 μmol/L had a significantly lower survival rate (logrank: 5.86; p=0.015). Levels of circulating ADMA might add diagnostic and prognostic information in CTEPH. Pulmonary endarterectomy is associated with an improvement in serum ADMA levels. Preoperative serum ADMA levels may be useful for estimating the outcome of PEA.

A systematic review of the correlation between serum asymmetric dimethylarginine, carotid atherosclerosis and ischaemic stroke.

To investigate the correlation between serum asymmetric dimethylarginine (ADMA) and the risk of ischaemic stroke and carotid atherosclerosis in adults. We systematically searched PubMed, EMBASE, Web of Science and other databases for relevant studies on serum ADMA and ischaemic stroke or carotid atherosclerosis, which were published from December 1980 to December 2019. The quality of the included studies was evaluated according to the Cochrane system evaluation standard. The difference in serum ADMA level between ischaemic stroke and control group was selected as the effect size (standardized mean difference, SMD). The pooled analysis was performed using Review Manager (V.5.3). According to the selection criteria, thirteen studies were included in the meta-analysis after screening. Nine studies compared ADMA levels between the ischaemic stroke group and healthy control group, involving a total of 1315 and 880 subjects in the two groups, respectively. Pooled effect sizes were calculated using the random-effects model due to the high heterogeneity (I2 =93%, P<.00001). The level of serum ADMA in patients with ischaemic stroke was significantly higher than that in healthy people (SDM=0.69, 95% CI [0.32, 1.06], P=.0002). Seven of the thirteen articles compared ADMA levels between the carotid arteriosclerosis group and the healthy control group, with 559 and 330 subjects in the two groups, respectively. The random-effects model was applied due to the high heterogeneity (I2 =91%, P<.00001). The level of serum ADMA in patients with carotid arteriosclerosis was significantly higher than that in healthy people (SDM=1.03, 95% CI [0.49, 1.57], P=.0002). The serum ADMA may be related to ischaemic stroke, and it is a risk factor for carotid atherosclerosis.

Asymmetric dimethylarginine: Is it a risk facgtor in the repair of aortic coarctation?

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, causes endothelial dysfunction which is an important risk factor for mortality in adult cardiovascular diseases. We aimed to investigate whether there was a relationship between the aortic cross-clamping (ACC) time and serum ADMA level in aortic coarctation surgery and importance of the serum ADMA level as a marker of mortality and morbidity. Twenty-two patients undergoing surgery for aortic coarctation in the neonatal and early infant period were included in the study, and the patients were divided into two groups according to the aortic cross-clamping time (Group I: <20-min, Group II: >20-min). In Group I, preoperative and postoperative mean ADMA values of the patients were 0.57 ± 0.78 and 0.54 ± 0.83 µmol/L, respectively. In Group II, preoperative and postoperative mean ADMA values of the patients were 0.69 ± 0.93 and 1.10 ± 0.30 µmol/L, respectively. Preoperative-postoperative change of ADMA correlates with ACC time (r = .802, p < .005) and duration of postoperative inotropic support (r = .719, p < .05). Also a high correlation has been found between the ACC time and duration of inotropic support in both groups (r = .689, p < .05). Perioperative serum ADMA levels could be used as a prognostic bio-marker in the patients undergoing aortic coarctation repair. Treatments to reduce serum ADMA levels can be valuable for preventing mortality and morbidity which develop after surgeries in a transient ischemia setting by clamping the aorta.

Association Between the Asymmetric Dimethylarginine Levels and Glaucoma Severity: A Cross-Sectional Analysis of the LIGHT Study.

PurposeAsymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of nitric oxide synthase, may be involved in the pathophysiology of glaucoma by dysfunctioning nitric oxide and oxidative stress. The purpose of this study was to determine whether the serum ADMA level is associated with the severity of glaucoma.MethodsOne hundred twenty-five patients with glaucoma (mean age 69.4 years) were analyzed in this cross-sectional study. The severity of glaucoma was determined by the visual field mean deviation in the worse eye; severe, a mean deviation ≤ −12 dB; and mild, a mean deviation > −12 dB. The serum ADMA levels were classified into three groups according to tertiles; low (T1), intermediate (T2), and high group (T3).ResultsThe mean serum ADMA levels in the severe glaucoma group was significantly higher than that in the mild glaucoma group (0.41 vs. 0.39 µmol/L; P = 0.031). A significantly higher prevalence of patients with severe glaucoma was found in the T3 group than that in the T1 group (T1, 44.7% and T3, 68.2%; P = 0.018). In the multivariable logistic regression analysis adjusted for the potential confounders, e.g., age, sex, obesity, smoking, hypertension, diabetes, and renal function, the odds ratio for severe glaucoma in the T3 group was significantly higher than that in the T1 group (odds ratio 3.02; 95% confidence interval 1.04 to 8.79; P = 0.043).ConclusionsA significant association between higher serum ADMA levels and severe glaucoma was found, and this association remained significant after adjusting for the potential confounders.

Endothelial Dysfunction and Atherosclerosis in Patients With Autosomal Dominant Polycystic Kidney Disease.

IntroductionIn this study, we aimed to determine the endothelial dysfunction (ED) and atherosclerosis in patients with autosomal dominant polycystic kidney disease (ADPKD).Materials and methodsThis study was conducted with 83 subjects (26 male, mean age: 46±11 years) consisted of three groups including ADPKD, hypertension (HT) and healthy control groups. The groups were evaluated in terms of serum endocan and asymmetric dimethylarginine (ADMA) levels, flow-mediated dilatation (FMD), nitroglycerin-mediated dilation (NMD) and carotid intima-media thickness (CIMT).ResultsSerum endocan and ADMA levels and CIMT were significantly higher while NMD was significantly lower in ADPKD group than control group. FMD and NMD were lower but serum ADMA level was higher in the ADPKD group than HT group; while serum endocan level and CIMT were not significantly different in ADPKD and HT groups. In ADPKD patients, CIMT value and serum endocan and ADMA levels were higher while NMD was lower in patients with eGFR≤60 mL/min/1.73 m2 than patients with eGFR>60 mL/min/1.73 m2. Serum ADMA level was higher and NMD was lower in hypertensive ADPKD patients than non-hypertensive ones. Serum endocan level was higher in ADPKD patients with nephrolithiasis and a negative correlation was detected between serum endocan level and 24-hour urine volume.ConclusionsEndothelial dysfunction and atherosclerosis are common conditions in ADPKD patients and it was further reinforced in our study. In order to clarify the relationship between serum endocan level and 24-hour urine volume, which is a remarkable finding in our study, larger studies that including the measurement of urine endocan may be useful.

Is there a relation between serum methylarginine levels and infertility?

Infertility is defined as the absence of pregnancy within the reproductive period despite regular sexual intercourse. Methylarginines are formed as a result of methylation of arginine residues in proteins and formed in three forms as asymmetric dimethyl arginine (ADMA), symmetrical dimethyl arginine (SDMA) and monomethylarginine (L-NMMA). So, here, we aimed to evaluate arginine and their derivatives levels in fertile and infertile individuals. Present study were consist of 30 oligozoospermia patients (proven by spermiogram analysis) and 30 healthy individuals with normozoospermia group who were applied to the urology department. With blood samples taken from individuals, serum methylarginine and its derivatives levels were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Clinic data and demographic characteristics of individuals were also recorded at the same time. The serum ADMA level (0.38±0.07) of the oligozoospermia group was found to be significantly higher than the normozoospermia group (0.35±0.05) (p=0.046). A positive correlation were observed between ADMA and SDMA (r=0.686, p=0.000), HArg and SDMA (r=0.611, p=0.001), citrulline and L-NMMA (r=0.595, p=0.001) in patients with oligosospermia. The increase in SDMA, arginine and HArg levels and a decrease in L-NMMA and citrulline levels were not significant as statistically. Also, the ADMA level was found to be high in individuals with low sperm concentration. Consequently, serum ADMA levels of individuals with oligozoospermia were statistically significantly higher than those with normozoospermia. As proposal, determination of ADMA levels may be a potential biomarker parameter in terms of early diagnosis of fertility and infertility.

Serum ADMA levels were positively correlated with EDSS scores in patients with multiple sclerosis

Multiple sclerosis (MS) is an autoinflammatory, chronic central nervous system disease. In the pathogenesis of the disease increased nitric oxide (NO) levels play an important role. Nitric oxide (NO) has neuroprotective effects in physiological conditions, however, it is thought that excessive NO formation in MS may lead to demyelination and axonal damage. Derivatives of methylarginine including asymmetric dimethyl arginine (ADMA), L-N monomethyl arginine (L-NMMA), symmetric dimethyl arginine (SDMA) directly or indirectly reduce NO production. Our aim was to measure the levels of methylarginine derivatives and citrulline, ornithine, arginine, homoarginine levels, which are metabolites associated with NO metabolism, in MS subgroups.

Relation of asymmetric dimethylarginine with pulmonary morbidities in neonatal respiratory distress syndrome.

Asymmetric Dimethyl Arginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) is important in different diseases characterized by decreased nitric oxide (NO) availability. We aimed to assess the serum ADMA level in preterm infants suffering from respiratory distress syndrome (RDS) and its relationship with pulmonary outcomes. This prospective study included 50 preterm neonates suffering from RDS aging≤32 weeks and weighing≤1500 gm. Serum ADMA levels were estimated in the 1st and 28th day of life by ELISA, and its correlation with surfactant requirement, duration of ventilation, and development of BPD was assessed. Fifty preterm infants with RDS were included, 30 infants were treated with surfactant within 12 hours after birth, the 1stday ADMA level was higher significantly in infants who required surfactant treatment than infants without surfactant treatment, At 36 weeks postmenstrual age, 16 infants were diagnosed with BPD, the 28th day ADMA level was significantly higher in infants with BPD than others without BPD. 1st-day ADMA level was significantly correlated with days on mechanical ventilation but there were no significant correlations between 1st day ADMA and days on CPAP and days on supplemental O2. Elevated serum ADMA level in preterm neonates with RDS estimated in the 1st and 28th day of life is a good predictor for pulmonary morbidities such as surfactant requirement, duration of mechanical ventilation, and development of BPD.

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.

The effect of α-lipoic acid treatment on plasma asymmetric dimethylarginine, a biomarker of endothelial dysfunction in diabetic neuropathy

IntroductionDiabetic neuropathy may develop on a background of hyperglycaemia and is associated with increased oxidative stress. Elevated asymmetric dimethylarginine (ADMA) levels are linked to oxidative stress reducing the synthesis of nitric oxide (NO) by uncoupling NO synthase. Oxidative stress induces considerable changes in nerve conduction velocity in diabetic patients. There is strong evidence that α-lipoic acid (ALA) as an antioxidant may improve nerve conduction and relieve neuropathic symptoms. We aimed to investigate the relationship between endothelial dysfunction and NO synthesis in type 2 diabetic patients with peripheral neuropathy after ALA treatment.Material and methodsFifty-four type 2 diabetic patients with neuropathy were included in the study. Serum ADMA concentration, ICAM-1, VCAM-1, oxidised low-density lipoprotein (oxLDL), and TNF-α levels were determined with Enzyme-Linked Immunosorbent Assay (ELISA). Nitric oxide concentration was measured by Griess reaction. Peripheral sensory nerve function was assessed by current perception threshold (CPT) testing. Autonomic function was assessed by Ewing’s five standard cardiovascular reflex tests composite autonomic score (CAS).ResultsAsymmetric dimethylarginine levels were significantly decreased (0.62 ±0.11 vs. 0.53 ±0.11 µmol/l, p &lt; 0.001), as well as TNF-α concentrations (1.21 ±0.42 pg/ml vs. 1.05 ±0.5 pg/ml, p &lt; 0.05), while NO levels were significantly increased (16.78 ±11.1 vs. 21.58 ±8.84 µmol/l, p &lt; 0.05) after six-months of 600 mg/day ALA treatment. VCAM-1, ICAM-1, and oxLDL levels did not change significantly. The CPT and CAS significantly improved after ALA treatment. The improvement of CPT values was correlated positively with the change of ADMA levels (r = 0.58, p &lt; 0.001). The change in ADMA level was more pronounced in responder patients based on both CPT and CAS.ConclusionsOur results suggest that ALA supplementation improves endothelial function characterised by serum levels of ADMA and TNF-α in patients with diabetic neuropathy. Changes in serum ADMA levels may predict the clinical response to ALA treatment.

The effects of melatonin against atherosclerosis-induced endothelial dysfunction and inflammation in hypercholesterolemic rats

The aim of this study was to investigate the effects of melatonin on the serum asymmetric dimethylarginine (ADMA) levels and the expressions of vaspin, visfatin, dimethylarginine dimethylaminohydrolase (DDAH), and signal transducer and activator of transcription-3 (STAT-3) for evaluation of endothelial function and inflammation in the hypercholesterolemic rats. Rats were divided into 5 groups: (1) control, (2) hypercholesterolaemia, (3) melatonin administrated concurrently with cholesterol diet, (4) melatonin administrated only last 2 weeks and fed with cholesterol diet, (5) atorvastatin administered only last 2 weeks fed with cholesterol diet. Although an increase was observed in the expressions of visfatin and STAT-3 and the serum ADMA levels, the vaspin and DDAH protein expressions were found to decrease with hypercholesterolemic diets. Melatonin was determined to restore all the parameters to the normal levels. In conclusion, melatonin may have protective and therapeutic effects on hypercholesterolaemia by regulating vaspin, STAT-3, DDAH, and ADMA signalling pathways and create similar effects with atorvastatin.

Role of Serum Asymmetric Dimethylarginine Level in Cardiovascular Diseases Early Prognostic in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome

The purpose of this paper was to investigate the role of serum asymmetric dimethylarginine (ADMA) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and identify its clinical significance in OSAHS related cardiovascular diseases. A total of 75 patients with OSAHS were enrolled and divided into mild (n=25), moderate (n=27), and severe group (n=23) according to their apnea hypopnea index (AHI) and minimal oxygen saturation (SaO2 min), respectively. Thirty healthy individuals were enrolled as normal control. Serum ADMA was measured with enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) level was assayed with colorimetric method. Nasal continuous positive airway pressure (nCPAP) treatment was performed to the patients, and the follow up lasted for 2 months. Serum ADMA level increased with the severity of patients. Serum NO level decreased with severity of patients. A negative correlation was noticed between serum NO and mean SaO2 (SaO2 mean) and minimal SaO2 (SaO2 min). Serum ADMA was positively correlated with AHI, tSaO2<90%, and morbidity of cardiovascular diseases. After nCPAP therapy, the serum ADMA level was remarkably decreased and NO was remarkably increased in patients with OSAHS. Serum ADMA may be correlated with OSAHS and OSAHS related cardiovascular diseases. Reducing the plasma ADMA level by nCPAP therapy can reduce the morbidity of OSAHS-related cardiovascular diseases.

Cardiovascular Biomarkers and Calculated Cardiovascular Risk in Orally Treated Type 2 Diabetes Patients: Is There a Link?

The aim of the study was to test the correlation of serum levels of asymmetric dimethylarginine (ADMA), endothelin 1 (ET-1), N-terminal brain natriuretic pro-peptide (NT-proBNP), and placental growth factor (PIGF-1) with estimated cardiovascular (CV) risk. The study group was composed of 102 women and 67 men with type 2 diabetes, having their glycemic and metabolic parameters assessed. All were on oral antidiabetic drugs. Serum levels of NT-proBNP and PIGF-1 were measured by electro-hemi-luminescence on an Elecsys 2010 analyzer. Enzymatic immunoassays were used for ADMA and ET-1. The Framingham Risk Score (FRS), the UKPDS 2.0 and the ADVANCE risk engines were used to calculate cardiovascular risks while statistical analysis was performed on SPSS. Levels of PIGF-1 showed no correlation with the calculated CV risks. The same was true for ADMA, except for a weak correlation with the UKPDS-based 10-year risk for stroke (Pearsons's R=0.167, p=0.039). Plasma levels of ET-1 were correlated with the UKPDS-based 10-year risk for stroke (R=0.184, p=0.032) and fatal stroke (R=0.215, p=0.012) only. NT-proBNP was significantly correlated with all CV risk calculations: ADVANCE-based 4-yr risk (Spearman's Rho=0.521, p<0.001); UKPDS-based 10-year risk for: CHD (Rho=0.209, p=0.01), fatal CHD (Rho=0.282, p<0.001), stroke (Rho=0.482, p<0.001), fatal stroke (Rho=0.505, p<0.001); and 10-year FRS risk (Rho=0.246, p=0.002). In conclusion, ADMA and PIGF-1 did not seem useful in stratifying CV risk while ET-1 is linked to the risk of stroke, and NT-proBNP to all CV risk estimations.

Serum LOX-1, ADMA and hs-CRP as Biomarkers of Ischemic Heart Disease in Chronic kidney Disease Patients

Abstracts Background: Ischemic heart disease (IHD) is the main cause of death in patients with chronic kidney disease (CKD)with coronary atherosclerosis , which could be predicted by inflammatory biomarkers , as high sensitive C-reactive protein (hs-CRP), IHD is linked to other independent risk factors as asymmetric dimethylarginine (ADMA) and lectin-like oxidized LDL receptor-1(LOX-1),which have proven roles in atherogenesis .objective to evaluate the clinical significance of ADMA and LOX-1 in addition to hs-CRP as biomarkers of IHD in ESRD patients with regular hemodialysis. Subjects and method: Patients groups included 27 patients under hemodialysis with known IHD (Subgroup Ia), 13 patients under hemodialysis without IHD (Subgroup Ib), 19 patients with CKD under conservative treatment (Subgroup Ic). And A control group of 29 healthy volunteers (group II) serum hs-CRP, ADMA, and LOX-1 were assayed. Results: the value of hs-CRP, ADMA and LOX-1 showed statistically significant increase in subgroup Ia versus subgroup Ib, also between subgroup Ib and subgroup Ic. Furthermore there is a highly statistical significant difference between different subgroups and control group. Correlation studies in subgroup Ia between hs-CRP, ADMA and LOX-1 revealed a statistically significant positive correlation. Conclusion: the combined use of hs-CRP and ADMA or LOX-1 showed to be valid for differentiating ESRD with IHD from ESRD without IHD. Serum levels of ADMA and LOX-1 could be relevant and convenient biomarkers for IHD in patients with CKD and its use beside hs-CRP adds more strength and specification to its known predictive value.

High Salt Intake Impairs Erectile Function in Salt-Sensitive Rats Through Mineralocorticoid Receptor Pathway Beyond Its Effect on Blood Pressure

BackgroundHigh salt intake is a risk factor for hypertension, which can potentially lead to erectile dysfunction (ED); however, the underlying pathological mechanisms remain unclear. AimTo investigate whether erectile function is directly impaired by high salt intake and whether selective inhibition of mineralocorticoid receptor (MR) could provide protection from ED. Methods6-week-old male Dahl salt-sensitive rats were randomly divided into 3 groups: normal diet (0.3% NaCl; control, n = 8), high-salt diet (8% NaCl; HS, n = 8), and high-salt diet plus eplerenone (HS + EPL, n = 11). HS + EPL rats were orally administered daily doses of EPL (75 mg/kg) for 6 weeks; control and HS rats received purified water on the same schedule. OutcomesAt the end of the study period, erectile function was evaluated by measuring intracavernosal pressure and mean arterial pressure after cavernous nerve stimulation. Serum levels of asymmetric dimethylarginine and L-arginine were determined using ultraperformance liquid chromatography–tandem mass spectrometry. Quantitative PCR was used to assess the expression of MR, inflammation, and oxidative stress markers (nicotinamide adenine dinucleotide phosphate oxidase-1/4, p22phox, interleukin-6, and superoxide dismutase-1), and protein arginine N-methyltransferase-1. ResultsThe intracavernosal pressure/mean arterial pressure ratio was significantly lower, whereas systolic blood pressure, MR expression, serum asymmetric dimethylarginine levels, oxidative stress, and levels of inflammatory biomarkers were significantly higher in HS rats than in control rats (P < .05). EPL administration significantly improved each of these parameters except systolic blood pressure and MR expression. No significant intergroup differences were observed for L-arginine and superoxide dismutase-1 levels. Clinical TranslationOur results provide a rationale for the need of salt restriction and the use of selective MR inhibitors in prophylaxis or treatment of ED in men consuming a high-salt diet. Strengths & LimitationsWe are the first to report that the adverse impact of high salt intake on erectile function is mediated via MR activation, independent of its effect on blood pressure. A major limitation of this study is that responses of salt-resistant rats were not studied. ConclusionsHigh salt intake directly impaired erectile function in Dahl salt-sensitive rats, whereas selective MR inhibition ameliorated this effect.Kishimoto T, Kataoka T, Yamamoto Y, et al. High Salt Intake Impairs Erectile Function in Salt-Sensitive Rats Through Mineralocorticoid Receptor Pathway Beyond Its Effect on Blood Pressure. J Sex Med 2020;17:1280–1287.

Serum asymmetric dimethylarginine, a novel risk marker of coronary artery disease

Coronary artery disease (CAD) is a chronic disease and a global health problem, affecting one-third of the world’s population. Recently it has been found that the traditional risk factors of CAD do not account for the total risk. One of the novel risk markers of CAD is Asymmetric dimethylarginine (ADMA), which inhibits the enzyme nitric oxide synthase (NOS), which is required for the synthesis of nitric oxide (NO), a potent vasodilator. Increased ADMA level causes decrease in NO level which will lead to endothelial dysfunction, an underlying causative mechanism for CAD development. ADMA is found to be an independent cardiovascular risk factor. Therefore ADMA may become an additional biochemical parameter to identify those patients who are at higher risk for developing CAD, besides the traditional parameters used.To study the association between serum ADMA level with coronary artery disease.The study design is a case-control study. 80 subjects from the south Indian population between 30 to 60 years of age, of both the sexes were included in the study. Out of them, 40 individuals were angiographically proven cases of CAD from the department of cardiology and 40 healthy individuals from the master health check up department. Various parameters like lipid profile, serum ADMA, blood pressure and BMI were measured in both the groups. The data were collected and analyzed.The ADMA level was found to be significantly elevated in the case group compared with the age matched healthy controls (p value &amp;#60; 0.05).There is a positive correlation between serum ADMA level and coronary artery disease.