Asymmetric Dimethylarginine Levels Research Articles

MO447PROTEIN ARGININE METHYLTRANSFERASE 3 INHIBITS RENAL INTERSTITIAL FIBROSIS THROUGH ENHANCING RENAL ASYMMETRIC DIMETHYLARGININE LEVELS

Abstract Background and Aims Mammalian Protein Arginine Methyltransferase 3 (PRMT3) catalyzes the monomethylation and dimethylation of the Arginine residues of proteins. The role of PRMT3 in renal fibrosis is currently unknown. We aimed to study the role of PRMT3 in renal fibrosis and explored its underlining mechanisms. Method Sham or Unilateral Ureter Obstruction (UUO) operation was performed in Prmt3 wild-type (WT), heterozygous (Het) and homozygous (Homo) mutant mice, which were sacrificed at day 14. A single dose of aristolochic acid (5mg/kg) was injected in WT or HE mice, which was sacrificed at day 42. Results A strong interstitial fibrosis was observed in WT UUO mice as shown by Masson staining, and heterozygous or homozygous deletion of Prmt3 gene further enhanced interstitial fibrosis in mouse kidneys. The expression of collagen-I in mouse kidneys were analyzed by Western blotting. UUO operation increased the expression of collagen-I in WT mouse kidneys, which were further increased by genetic deletion of Prmt3 gene in a dose-dependent manner. A mild renal interstitial fibrosis was observed in AAN mice, which was enhanced by heterozygous deletion of Prmt3 gene. Western blot analysis showed that aristolochic acid increased the expression of collagen-I in WT mice, which was further increased in Prmt3 Het mutant mice. Mechanismly, asymmetric dimethylarginine levels were elevated in UUO or AAN mouse kidneys as compared with its controls as shown by immnohistochemistry staining or ELISA. Renal ADMA levels were not elevated in Prmt3 mutant UUO or AAN mice. Moreover, renal injection of ADMA in UUO kidneys blocked the enhanced renal interstitial fibrosis in Prmt3 Het mutant mice as shown by Masson staining and Western blot analysis of collagen-I. Conclusion Prmt3 inhibits renal interstitial fibrosis through enhancing renal ADMA levels.

MO099REPROGRAMMING HYPERTENSION PROGRAMMED BY HIGH-FAT DIET: THE ROLE OF GARLIC OIL

Abstract Background and Aims Perinatal high-fat (HF) diet programs high blood pressure (BP) in adult offspring. Hydrogen sulfide (H2S) has shown benefits in hypertension by restoration of nitric oxide (NO) bioavailability and alterations of gut microbiota. Garlic, a naturally dietary source of H2S donors, supplementation has shown benefits in hypertension. We aimed to examine whether maternal garlic oil supplementation can prevent hypertension programmed by maternal and post-weaning high-fat diet in adult offspring and whether its protective effects are related to mediation of H2S-genetaing system, alterations of gut microbiota composition, and microbiota metabolite short chain fatty acids (SCFAs). Method Pregnant rats received either a normal diet (ND) or HF diet (D12331, Research Diets, Inc.) Garlic oil (GO) or vesicle was administered daily by oral gavage at 100 mg/kg/day during pregnancy and lactation. Male offspring were weaned at 3 weeks of age, and onto either ND or HF diet to 16 weeks of age. Male offspring were assigned to four groups (n=8/group): ND, HF, ND+GO, and HF+GO. Garlic supplementation during pregnancy and lactation protected against programmed hypertension in adult male offspring fed with HF diet. All offspring were killed at 16 weeks of age. NO-related parameters were analyzed by HPLC. Plasma levels of SCFA were determined using GC-MS method. Fecal microbial community was analyzed using a combination of 16S rRNA gene and fecal metagenome sequence analysis. Results Garlic supplementation during pregnancy and lactation protected against programmed hypertension in adult male offspring fed with HF diet. Garlic oil supplementation caused a significant increase in plasma levels of acetate, propionate, and butyrate. NO bioavailability was augmented by garlic oil supplementation, represented by decreases of plasma levels of asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels, and increased plasma L-arginine-to-ADMA ratio (AAR). HF intake associated with decreased α-diversity was quantified by Shannon diversity index. The Analysis of similarities (ANOSIM) demonstrated the difference in the gut microbiota among the four groups existed (All p < 0.05), indicating that four groups had distinct enterotypes. Additionally, garlic oil supplementation increased abundance of genus Lactobacillus, but decreased genera Turicibacter and Staphylococcus. Moreover, the linear discriminant analysis effect size (LEfSe) algorithm analysis identified several microbial markers including genera Lactobacillus, Staphylococcus, and Turicibacter. Conclusion The beneficial effects of garlic oil were associated with increased renal mRNA expression and activity of H2S-generating enzymes, increased NO bioavailability, increased plasma SCFA levels, and alterations of gut microbiota composition. Our data revealed associations between H2S-generating pathway in the gut and kidneys, NO system, gut microbiota, and microbiota-derived metabolites in hypertension programmed by HF intake and provided insight to garlic oil as a hypertension reprogramming strategy for further translational research.

Elevated asymmetric dimethylarginine level as biomarkers of adverse outcomes in individuals undergoing coronary angiography/percutaneous coronary interventions: a systematic review and meta-analysis

No previous systematic review and meta-analysis have comprehensively evaluated the association of asymmetric dimethylarginine (ADMA) level with adverse prognosis in individuals undergoing percutaneous coronary interventions (PCI)/coronary angiography (CAG). The aim of this systematic review and meta-analysis was to assess the predictive value of the elevated ADMA level in individuals undergoing CAG/PCI. Two authors independently searched PubMed and Embase databases (up to 31 October 2020) for observational studies investigating the association between circulating ADMA level and adverse outcomes in individuals undergoing CAG/PCI. The predictive value of ADMA was expressed by pooling the multivariable-adjusted risk ratio with 95% confidence intervals (CI) for the highest versus lowest ADMA level. A total of nine prospective studies with 6374 participants were identified. Compared with those with the lowest ADMA level, patients with the highest ADMA level conferred an increased risk of all-cause mortality (risk ratio, 2.11; 95% CI, 1.38-3.21), cardiovascular mortality (risk ratio, 2.95; 95% CI, 1.14-7.68), major adverse cardiovascular events (risk ratio, 2.10; 95% CI, 1.35-3.27) and restenosis (risk ratio, 4.57; 95% CI, 2.52-8.30), respectively. High level of ADMA level is possibly an independent predictor of mortality and cardiovascular events in individuals undergoing CAG/PCI. Detection of blood ADMA level before CAG/PCI may add valuable clinical prognosis information.

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.

Biomarkers representing key aging-related biological pathways are associated with subclinical atherosclerosis and all-cause mortality: The Framingham Study.

Increased oxidative stress, leukocyte telomere length (LTL) shortening, endothelial dysfunction, and lower insulin-like growth factor (IGF)-1 concentrations reflect key molecular mechanisms of aging. We hypothesized that biomarkers representing these pathways are associated with measures of subclinical atherosclerosis and all-cause mortality. We evaluated up to 2,314 Framingham Offspring Study participants (mean age 61 years, 55% women) with available biomarkers of aging: LTL, circulating concentrations of IGF-1, asymmetrical dimethylarginine (ADMA), and urinary F2-Isoprostanes indexed to urinary creatinine. We evaluated the association of each biomarker with coronary artery calcium [ln (CAC+1)] and carotid intima-media thickness (IMT). In multivariable-adjusted linear regression models, higher ADMA levels were associated with higher CAC values (βADMA per 1-SD increase 0.25; 95% confidence interval [CI] [0.11, 0.39]). Additionally, shorter LTL and lower IGF-1 values were associated with higher IMT values (βLTL -0.08, 95%CI -0.14, -0.02, and βIGF-1 -0.04, 95%CI -0.08, -0.01, respectively). During a median follow-up of 15.5 years, 593 subjects died. In multivariable-adjusted Cox regression models, LTL and IGF-1 values were inversely associated with all-cause mortality (hazard ratios [HR] per SD increase in biomarker, 0.85, 95% CI 0.74-0.99, and 0.90, 95% CI 0.82-0.98 for LTL and IGF-1, respectively). F2-Isoprostanes and ADMA values were positively associated with all-cause mortality (HR per SD increase in biomarker, 1.15, 95% CI, 1.10-1.22, and 1.10, 95% CI, 1.02-1.20, respectively). In our prospective community-based study, aging-related biomarkers were associated with measures of subclinical atherosclerosis cross-sectionally and with all-cause mortality prospectively, supporting the concept that these biomarkers may reflect the aging process in community-dwelling adults.

Homoarginine and methylarginines independently predict long-term outcome in patients presenting with suspicion of venous thromboembolism

Endogenous arginine derivatives homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethyarginine (SDMA) are independent mortality predictors in atherosclerotic cardiovascular disease (CVD). Our study reports the first analysis, whether homoarginine, ADMA and SDMA predict venous thromboembolism (VTE) recurrence and overall mortality in patients with suspected acute VTE. We assessed serum levels of homoarginine, ADMA and SDMA by LC–MS/MS in 865 individuals from a prospective consecutive cohort of patients with clinical suspicion of VTE. The median follow-up time for mortality was 1196 days. VTE was confirmed by imaging in 418 patients and excluded in 447 patients. Low levels of homoarginine and high levels of ADMA or SDMA independently predicted all-cause mortality after adjustment for sex, age, oral anticoagulants, body mass index, arterial hypertension, diabetes mellitus, smoking, dyslipidemia, chronic heart failure, history of stroke, creatinine and cancer both in patients with VTE and without VTE. Interestingly, none of those parameters was predictive for VTE recurrence. We provide the first report that low circulating levels of homoarginine and high circulating levels of ADMA and SDMA independently predict all-cause mortality in patients with suspected VTE. These parameters might serve as markers of “frailty” and should be considered for future risk stratification approaches in this clinical population. Taking into account that homoarginine supplementation is protective in animal models of CVD and safe in healthy human volunteers, our study provides the basis for future homoarginine supplementation studies in patients with suspected VTE to investigate possible direct protective effects of homoarginine in this population.

Nandina domestica Leaf Extracts Ameliorate Lung Injury by Decreasing Inflammatory Cytokine Levels and Neutrophil Accumulation in Mice Injected with Fine Dust

Exposure to dust particles can lead to respiratory problems, diseases, and even death. In this study, we examined the effects of Nandina domestica (ND) on bronchoalveolar lavage fluid (BALF) and lung of intra-nazal-trachea (INT) injected mice with fine dust mixture of coal, flay ash and diesel exhausted particle (CFD). ND significantly reduced the counts of neutrophils in BALF and histological changes in lung tissues including infiltration of inflammatory cells and goblet cell hyperplasia with lowering lung injury score and periodic acid Schiff (PAS) score. In addition, the elevated inflammatory cytokines such as interleukin (IL)-17 and tumor necrosis factor-α (TNF-α) in BALF, macrophage inflammatory protein-2 (MIP-2) and C-X-C motif chemokine 1 (CXCL-1) significantly decreased to a greater extent by ND treatment. Furthermore, ND significantly decreased levels of asymmetric dimethyl-arginine (ADMA) and symmetric dimethyl-arginine (SDMA) elevated by CFD in BALF. Therefore, these data suggest that ND ameliorated lung injury by suppressing inflammatory cytokines as well as by reducing the accumulation of neutrophils.

Nandina domestica Leaf Extracts Ameliorate Lung Injury by Decreasing Inflammatory Cytokine Levels and Neutrophil Accumulation in Mice Injected with Fine Dust

Exposure to dust particles can lead to respiratory problems, diseases, and even death. In this study, we examined the effects of Nandina domestica (ND) on bronchoalveolar lavage fluid (BALF) and lung of intra-nazal-trachea (INT) injected mice with fine dust mixture of coal, flay ash and diesel exhausted particle (CFD). ND significantly reduced the counts of neutrophils in BALF and histological changes in lung tissues including infiltration of inflammatory cells and goblet cell hyperplasia with lowering lung injury score and periodic acid Schiff (PAS) score. In addition, the elevated inflammatory cytokines such as interleukin (IL)-17 and tumor necrosis factor-α (TNF-α) in BALF, macrophage inflammatory protein-2 (MIP-2) and C-X-C motif chemokine 1 (CXCL-1) significantly decreased to a greater extent by ND treatment. Furthermore, ND significantly decreased levels of asymmetric dimethyl-arginine (ADMA) and symmetric dimethyl-arginine (SDMA) elevated by CFD in BALF. Therefore, these data suggest that ND ameliorated lung injury by suppressing inflammatory cytokines as well as by reducing the accumulation of neutrophils.

Metabolome and lipidome derangements during a severe mast cell activation event in a patient with indolent systemic mastocytosis

The number of mast cells in various organs is elevated manifold in individuals with systemic mastocytosis. Degranulation can lead to life-threatening symptomatology. No data about the alterations of the metabolome and lipidome during an attack have been published. Our aim was to analyze changes in metabolomics and lipidomics during the acute phase of a severe mast cell activation event. A total of 43 metabolites and 11 lipid classes comprising 200 subvariants from multiple plasma samples in duplicate, covering 72 hours of a severe mast cell activation attack with nausea and vomiting, were compared with 2 baseline samples by using quantitative liquid chromatography-mass spectrometry. A strong enterocyte dysfunction reflected in an almost 20-fold reduction in the functional small bowel length was extrapolated from strongly reduced ornithine and citrulline concentrations and was very likely secondary to severe endothelial cell dysfunction with hypoperfusion and extensive vascular leakage. Highly increased histamine and lactate concentrations accompanied the peak in clinical symptoms. Elevated asymmetric and symmetric dimethylarginine levels combined with reduced arginine levels compromised endothelial nitric oxide synthase activity and nitric oxide signaling. Specific and extensive depletion of many lysophosphatidylcholine variants indicates localized autotaxin activation and lysophosphatidic acid release. Astrong correlation of clinical parameters with histamine concentrations and symptom reduction after 100-fold elevated plasma diamine oxidase concentrations implies that histamine is the key driver of the acute phase. Rapid elimination of elevated histamine concentrations through use of recombinant human diamine oxidase, supplementation of lysophosphatidylcholine for immunomodulation, inhibition of autotaxin activity, and/or blockade of lysophosphatidic acid receptors might represent new treatment options for life-threatening mast cell activation events.

The Role of Oxidative Stress Markers in Predicting Acute Thrombotic Occlusion of Haemodialysis Vascular Access and Progressive Stenotic Dysfunction Demanding Angioplasty.

Haemodialysis vascular access (VA) dysfunction is a major cause of morbidity in haemodialysis (HD) patients. Primary venous outflow occlusion and restenosis after percutaneous transluminal angioplasty (PTA) are two major obstacles for the long-term use of dialysis VA. It remains unclear whether oxidative stress markers can be used as predictors for thrombotic occlusion of VA and progressive stenosis dysfunction demanding PTA. All routine HD patients at one teaching hospital participated in this study including ankle-brachial index (ABI) examinations and serum oxidative stress markers. The serum oxidative stress markers (high-sensitivity C-reactive protein (hs-CRP), matrix metalloproteinase-2 (MMP-2), MMP-9, homocysteine, asymmetrical dimethylarginine (ADMA), nitrate oxidase (NO), tumour necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), interleukin-1β (IL-1β), and transforming growth factor-β (TGF-β)) were measured using immunosorbent assays in 159 HD patients (83 men and 76 women; mean age: 65 ± 12 years). The participants met the following criteria: (1) received regular HD treatment for at least 6 months, without clinical evidence of acute or chronic inflammation, recent myocardial infarction, unstable angina or circulatory congestion; and (2) received an arteriovenous fistula (AVF)/arteriovenous graft (AVG: polytetrafluoroethylene, PTFE) as the current VA for more than 6 months, without interventions within the last 6 months. All the participants were followed up clinically for up to 12 months to estimate the amount of primary thrombotic occlusion and VA dysfunction demanding PTA. During the 12-month observation, 24 patients (15.1%) had primary thrombotic occlusion of VAs. Another 24 patients (15.1%) required PTA because of clinical dysfunction of access. Additionally, during the follow-up period, restenosis occurred in 12 patients (50% of 24 patients). The access types of arteriovenous grafts (AVGs) and a diagnosis of peripheral arterial occlusive disease (PAOD) were two strong predictors for acute thrombotic events of VA (hazard ratio (HR): 16.93 vs. 2.35; p < 0.001 vs. 0.047). Comparing dysfunctional with non-dysfunctional VAs, up to 27.7% of patients with high levels of ADMA (>0.6207 μM, N = 65) received required PTA compared with 4.4% of those with low levels (≤0.6207 μM; N = 90; p < 0.001). In multivariate analysis, the plasma baseline levels of ADMA independently conferred nearly 4.55 times the risk of primary stenotic dysfunction of HD VA (HR: 4.55; 95% confidence interval: 1.20 to 17.26; p = 0.026). In conclusion, our findings suggest the role of ADMA in the development of symptomatic VA dysfunction. Additionally, PAOD severity can be used in clinical practice to predict whether acute thrombotic occlusion of VA will easily occur in HD patients.

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.

Relationship between plasma asymmetric dimethylarginine and nitric oxide levels affects aerobic exercise training-induced reduction of arterial stiffness in middle-aged and older adults.

[Purpose]Aerobic exercise training (AT) reverses aging-induced deterioration of arterial stiffness via increased arterial nitric oxide (NO) production. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, was decreased by AT. However, whether AT-induced changes in ADMA levels are related to changes in nitrite/nitrate (NOx) levels remains unclear. Accordingly, we aimed to clarify whether the relationship between plasma ADMA and NOx levels affected the AT-induced reduction of arterial stiffness in middle-aged and older adults.[Methods]Thirty-one healthy middle-aged and older male and female subjects (66.4 ± 1.3 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed an 8-week AT (60%–70% peak oxygen uptake [] for 45 min, 3 days/week).[Results]AT significantly increased (p < 0.05) and decreased carotid β-stiffness (p < 0.01). Moreover, plasma ADMA levels were significantly decreased while plasma NOx levels and NOx/ADMA ratio were significantly increased by AT (p < 0.01). Additionally, no sex differences in AT-induced changes of circulating ADMA and NOx levels, NOx/ADMA ratio, and carotid β-stiffness were observed. Furthermore, the AT-induced increase in circulating ADMA levels was negatively correlated with an increase in circulating NOx levels (r = -0.414, p < 0.05), and the AT-induced increase in NOx/ADMA ratio was negatively correlated with a decrease in carotid β-stiffness (r = -0.514, p < 0.01).[Conclusion]These results suggest that the increase in circulating NOx with reduction of ADMA elicited by AT is associated with a decrease in arterial stiffness regardless of sex in middle-aged and older adults.

EVALUATION OF INFLAMMATION AND ENDOTHELIAL DYSFUNCTION BIOMARKERS IN CHRONIC KIDNEY DISEASE (CKD) PATIENTS IN SOKOTO, NIGERIA

Inflammation and endothelial dysfunction have been known to be involved in the pathogenesis of cardiovascular diseases. As such, examining the levels of inflammation and endothelial dysfunction is very critical to the prevention of cardiovascular diseases among chronic kidney disease (CKD) patients. This study aimed to investigate the progression of inflammation and endothelial dysfunction among CKD patients in Sokoto. A total of 67 CKD patients were divided into 5 groups based on the stages of their kidney disease calculated using the MDRD 4-variable equation for estimated glomerular filtration rate (eGFR). The presence of inflammation was determined by C-Reactive Protein (CRP) and Tumor Necrosis Factor alpha, while endothelial dysfunction was determined by the levels of Asymmetric dimethylarginine (ADMA) using ELISA kits. The mean eGFR of the patients was 49.97 ± 4.69 ml/min/1.73m2. There was significant increase (p&lt;0.05) in CRP, TNF-α and ADMA of the CKD patients across the stages as compared to the non-CKD subjects. It was observed that as the CRP, TNF-α and ADMA increase, the eGFR significantly (p&lt;0.05) decreases. Both CRP and TNF-α indicated a significantly positive correlation (p&lt;0.05) with ADMA. The results indicated progressive increase in inflammation and endothelial dysfunction as CKD deteriorates. In addition, increased levels of inflammation could directly affect endothelial dysfunction, thereby aggravating cardiovascular morbidity and mortality among CKD patients in Sokoto.&#x0D; Otitolaiye, C. A. | Department of Biochemistry, Sokoto State University, Sokoto, Nigeria

Asymmetric dimethylarginine in psychiatric disorders

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

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

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

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.

Altered methylarginine levels after surgery in subjects with multinodular goiter.

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

Impact of combined elevations of homocysteine and asymmetric dimethylarginine on all-cause death ― The Tanushimaru Study

BackgroundBoth homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) induce endothelial dysfunction. However, the impact of both elevations on all-cause death is not known. We investigated the association between elevations of Hcy or ADMA and all-cause death in a general population. MethodsA total of 517 subjects (224 men, 293 women; mean age, 62.8 years) were recruited from a population-based survey in 1999 in Tanushimaru, and we measured fasting plasma Hcy and ADMA levels. We followed them up for over 20 years and examined the effect on mortality using Cox proportional hazard regression model. ResultsThe mean follow-up years were 17.7 (1.8-20.8). In this period, 182 subjects have died (35.2%). The correlation between Hcy and ADMA was high (r=0.194; p<0.001). With Cox regression analysis after adjustments for age and sex, elevated log transformed Hcy levels were significantly associated with all-cause death (p=0.028). When Hcy and ADMA levels were divided into quintiles, the hierarchical model showed the synergistic effect of Hcy and ADMA on all-cause death. ConclusionsThis is the first report that we have measured Hcy and ADMA levels simultaneously in this community-dwelling Japanese, and we demonstrated that combined elevations of Hcy and ADMA had big impact on all-cause death in this epidemiological study.

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

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

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.