scholarly journals Asymmetric Dimethylarginine in Patients with Ascending Aortic Aneurysms

Aorta ◽  
2016 ◽  
Vol 04 (06) ◽  
pp. 219-225 ◽  
Author(s):  
Natalia Gavriliuk ◽  
Tatiana Druzhkova ◽  
Olga Irtyuga ◽  
Alexandr Zhloba ◽  
Tatiana Subbotina ◽  
...  
Keyword(s):  
High Performance ◽  
Asymmetric Dimethylarginine ◽  
Estimated Glomerular Filtration Rate ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Plasma Adma ◽  
Multivariable Regression Model ◽  
Multivariable Regression ◽  
Synthase Inhibitor ◽  
Ascending Aortic Diameter

Background: Ascending thoracic aortic aneurysm (aTAA) is a heterogeneous group of disorders that involve impaired endothelial function. The nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) serves as an endothelial dysfunction marker. Thus, we investigated ADMA levels in patients with aTAA. Methods: Eighty-six patients with aTAA and 18 healthy individuals were enrolled. All patients underwent echocardiography. Plasma ADMA levels were measured using high-performance liquid chromatography. Results: ADMA levels were higher in aTAA patients than in control patients (p = 0.034). According to the multivariable regression model, higher ADMA levels were associated with ascending aortic diameter (p = 0.017), smoking (p = 0.016), and log-transformed estimated glomerular filtration rate (eGFR, p = 0.005). Conclusion: This pilot study demonstrates an association of ADMA with ascending aortic dilatation; however, further studies are needed to investigate whether increased ADMA levels underlie aTAA development.

scholarly journals The Functional Polymorphism of DDAH2 rs9267551 Is an Independent Determinant of Arterial Stiffness

2022 ◽  
Vol 8 ◽  
Author(s):  
Carolina Averta ◽  
Elettra Mancuso ◽  
Rosangela Spiga ◽  
Sofia Miceli ◽  
Elena Succurro ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Gold Standard ◽  
Asymmetric Dimethylarginine ◽  
Pulse Wave ◽  
European Ancestry ◽  
Causative Role ◽  
Gold Standard Method ◽  
Multivariable Regression Model ◽  
Multivariable Regression ◽  
Independent Determinant

Background: The association of circulating asymmetric dimethylarginine (ADMA) levels with cardiovascular risk and arterial stiffness has been reportedly demonstrated, although the causal involvement of ADMA in the pathogenesis of these conditions is still debated. Dimethylaminohydrolase 2 (DDAH2) is the enzyme responsible for ADMA hydrolysis in the vasculature, and carriers of the polymorphism rs9267551 C in the 5′-UTR of DDAH2 have been reported to have higher DDAH2 expression and reduced levels of serum ADMA.Approach and Results: We genotyped rs9267551 in 633 adults of European ancestry and measured their carotid–femoral pulse wave velocity (cfPWV), the gold-standard method to estimate arterial stiffness. cfPWV resulted significantly lower in rs9267551 C allele carriers (Δ = −1.12 m/s, P < 0.01) after correction for age, sex and BMI, and a univariate regression showed that the presence of rs9267551 C variant was negatively associated with cfPWV (β = −0.110, P < 0.01). In a multivariable regression model, subjects carrying the rs9267551 C allele manifested significantly lower cfPWV than GG carriers (β = −0.098, P = 0.01) independently from several potential confounders. We measured circulating ADMA levels in a subset of 344 subjects. A mediation analysis revealed that the effect of DDAH2 rs9267551 genotype on cfPWV was mediated by the variation in ADMA levels.Conclusions: These evidences hint that the presence of rs9267551 C allele may explain, at least in part, a reduction in vessel rigidity as measured by cfPWV, and support the attribution of a causative role to ADMA in the pathogenesis of arterial stiffness.

Endothelin stimulates an endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine, in experimental heart failure

2002 ◽  
Vol 103 (s2002) ◽  
pp. 241S-244S ◽  
Author(s):  
Masato OHNISHI ◽  
Atsuyuki WADA ◽  
Takayoshi TSUTAMOTO ◽  
Masanori FUJII ◽  
Takehiro MATSUMOTO ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Vascular Resistance ◽  
Vascular Tone ◽  
Asymmetric Dimethylarginine ◽  
No Production ◽  
Plasma Adma ◽  
Eta Receptor ◽  
Eta Receptor Antagonist ◽  
Synthase Inhibitor ◽  
Regulation Of Vascular Tone

Congestive heart failure (CHF) is characterized by increased peripheral vascular resistance. Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor, is present at increased concentrations in the plasma and contributes to the regulation of vascular tone in CHF. An endothelium-derived relaxing factor, nitric oxide (NO), also regulates vascular tone, but endothelium-dependent NO-mediated vasodilation is blunted in CHF. An endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), which inhibits NO production and endothelium-dependent relaxation, is present at increased levels in the plasma and plays a role in impaired endothelial function in CHF. However, at present, the relationship between ET-1 and impaired vascular relaxation in CHF is not well known. We hypothesized that ET-1 inhibits NO-mediated vasodilation via increased ADMA production in CHF, and that an endothelin receptor antagonist can prevent this increase in plasma ADMA levels. In the present study, we first examined whether circulating ADMA levels were increased in a dog model of CHF induced by 3 weeks of rapid ventricular pacing (n = 5; 270beats/min) compared with normal dogs (n = 5). After 3 weeks of pacing, cardiac output had decreased significantly (1.56±0.16 compared with 2.93±0.25litres/min; P<0.01) and systemic vascular resistance had increased (4653±374 compared with 3227±396dyn·s·cm-5; P<0.01) in dogs with CHF compared with normal dogs. Plasma levels of both ET-1 (4.95±0.83 compared with 2.12±0.39pg/ml; P<0.05) and ADMA (3.27±0.49 compared with 1.91±0.25nmol/ml; P<0.05) were significantly increased in CHF dogs. A significant positive correlation was observed between plasma ET-1 and ADMA levels (r = 0.72, P<0.05). Secondly, we chronically administered an ETA receptor antagonist, TA-0201 (0.3mg/kg; n = 5), to paced CHF dogs. Drug administration started on day 8 of pacing and continued throughout the experiment. TA-0201 significantly increased cardiac output (2.58±0.24litres/min; P<0.01) and suppressed the increases in plasma ADMA levels and systemic vascular resistance (2.36±0.30nmol/ml and 2423±188dyn·s·cm-5 respectively; P<0.05 for each) compared with CHF dogs without TA-0201 treatment. In conclusion, ET-1 contributes to the regulation of vascular tone due, in part, to increased levels of an endogenous NO synthase inhibitor in CHF, and an ETA receptor antagonist can prevent the inhibition of NO production and the increased peripheral vascular resistance observed in CHF.

Role of the human erythrocyte in generation and storage of asymmetric dimethylarginine

2012 ◽  
Vol 302 (8) ◽  
pp. H1762-H1770 ◽  
Author(s):  
Mariska Davids ◽  
Albert J. van Hell ◽  
Marlieke Visser ◽  
Robert J. Nijveldt ◽  
Paul A. M. van Leeuwen ◽  
...  
Keyword(s):  
Human Erythrocyte ◽  
Asymmetric Dimethylarginine ◽  
Nitric Oxide Synthase Inhibitor ◽  
Plasma Adma ◽  
Erythrocyte Lysis ◽  
Endogenous Nitric Oxide ◽  
Complete Lysis ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Proteolytic activity in whole blood may lead to release of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). We investigated the role of the human erythrocyte in storage and generation of ADMA in healthy controls ( n = 36) and critically ill patients ( n = 38). Both free and total (sum of free and protein-incorporated) ADMA were measured. Upon incubation of intact erythrocytes with extracellular ADMA (0 to 40 μmol/l), equilibrium between intra- and extracellular ADMA was reached within 3 h. Compared with controls, patients had significantly higher basal concentrations of ADMA in plasma (0.88 ± 0.75 vs. 0.41 ± 0.07 μmol/l) and erythrocytes (1.28 ± 0.55 vs. 0.57 ± 0.14 μmol/l). Intracellular and plasma ADMA were significantly correlated in the patient group only ( r = 0.834). Upon lysis, followed by incubation at 37°C for 2 h, free ADMA increased sevenfold (to 8.60 ± 3.61 μmol/l in patients and 3.90 ± 0.78 μmol/l in controls). In lysates of controls, free ADMA increased further to 9.85 ± 1.35 μmol/l after 18 h. Total ADMA was 15.43 ± 2.44 μmol/l and did not change during incubation. The increase of free ADMA during incubation corresponded to substantial release of ADMA from the erythrocytic protein-incorporated pool (21.9 ± 4.6% at 2 h and 60.8 ± 7.6% at 18 h). ADMA was released from proteins other than hemoglobin, which only occurred after complete lysis and was blocked by combined inhibition of proteasomal and protease activity. Neither intact nor lysed erythrocytes mediated degradation of free ADMA. We conclude that intact erythrocytes play an important role in storage of ADMA, whereas upon erythrocyte lysis large amounts of free ADMA are generated by proteolysis of methylated proteins, which may affect plasma levels in hemolysis-associated diseases.

Glutathione system participation in thoracic aneurysms from patients with Marfan syndrome

VASA ◽  
2017 ◽  
Vol 46 (3) ◽  
pp. 177-186 ◽  
Author(s):  
Alejandra María Zúñiga-Muñoz ◽  
Israel Pérez-Torres ◽  
Verónica Guarner-Lans ◽  
Elías Núñez-Garrido ◽  
Rodrigo Velázquez Espejel ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Marfan Syndrome ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Glutathione S Transferase ◽  
Reduced And Oxidized Glutathione ◽  
Total Antioxidant ◽  
Elevated Activity ◽  
Acute Dissection ◽  
Thoracic Aneurysms

Abstract. Background: Aortic dilatation in Marfan syndrome (MFS) is progressive. It is associated with oxidative stress and endothelial dysfunction that contribute to the early acute dissection of the vessel and can result in rupture of the aorta and sudden death. We evaluated the participation of the glutathione (GSH) system, which could be involved in the mechanisms that promote the formation and progression of the aortic aneurysms in MFS patients. Patients and methods: Aortic aneurysm tissue was obtained during chest surgery from eight control subjects and 14 MFS patients. Spectrophotometrical determination of activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO) index, carbonylation, total antioxidant capacity (TAC), and concentration of reduced and oxidized glutathione (GSH and GSSG respectively), was performed in the homogenate from aortic aneurysm tissue. Results: LPO index, carbonylation, TGF-β1, and GR activity were increased in MFS patients (p < 0.04), while TAC, GSH/GSSG ratio, GPx, and GST activity were significantly decreased (p < 0.04). Conclusions: The depletion of GSH, in spite of the elevated activity of GR, not only diminished the activity of GSH-depend GST and GPx, but increased LPO, carbonylation and decreased TAC. These changes could promote the structural and functional alterations in the thoracic aorta of MFS patients.

scholarly journals Fatigue among children with a chronic disease: a cross-sectional study

2021 ◽  
Vol 5 (1) ◽  
pp. e000958
Author(s):  
Merel M Nap-van der Vlist ◽  
Geertje W Dalmeijer ◽  
Martha A Grootenhuis ◽  
Kors van der Ent ◽  
Marry M van den Heuvel-Eibrink ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Social Factors ◽  
Participation Rate ◽  
Cross Sectional Study ◽  
Assessment Tools ◽  
Sectional Study ◽  
Cross Sectional ◽  
Multivariable Regression Model ◽  
Multivariable Regression ◽  
Multidimensional Fatigue Scale

ObjectiveTo determine: (1) which biological/lifestyle, psychological and/or social factors are associated with fatigue among children with a chronic disease and (2) how much each of these factors contributes to explaining variance in fatigue.Design and settingThis was a cross-sectional study across two children’s hospitals.PatientsWe included children aged 8–18 years who visited the outpatient clinic with cystic fibrosis, an autoimmune disease or postcancer treatment.Main outcome measuresFatigue was assessed using the PedsQL Multidimensional Fatigue Scale. Generic biological/lifestyle, psychological and social factors were assessed using clinical assessment tools and questionnaires. Multiple linear regression analyses were used to test the associations between these factors and fatigue. Finally, a multivariable regression model was used to determine which factor(s) have the strongest effect on fatigue.ResultsA total of 434 out of 902 children were included (48% participation rate), with a median age of 14.5 years; 42% were male. Among these 434 children, 21.8% were severely fatigued. Together, all biopsychosocial factors explained 74.6% of the variance in fatigue. More fatigue was uniquely associated with poorer physical functioning, more depressive symptoms, more pressure at school, poorer social functioning and older age.ConclusionsFatigue among children with a chronic disease is multidimensional. Multiple generic biological/lifestyle, psychological and social factors were strongly associated with fatigue, explaining 58.4%; 65.8% and 50.0% of the variance in fatigue, respectively. Altogether, almost three-quarters of the variance in fatigue was explained by this biopsychosocial model. Thus, when assessing and treating fatigue, a transdiagnostic approach is preferred, taking into account biological, psychological and social factors.

scholarly journals Quantitative not qualitative histology differentiates aneurysmal from nondilated ascending aortas and reveals a net gain of medial components

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sameh Yousef ◽  
Nana Matsumoto ◽  
Issam Dabe ◽  
Makoto Mori ◽  
Alden B. Landry ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Quantitative Assessment ◽  
Cell Number ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Adaptive Responses ◽  
Cross Sectional ◽  
Thoracic Aortic Aneurysms ◽  
Medial Degeneration ◽  
The Media

AbstractMedial degeneration is a common histopathological finding in aortopathy and is considered a mechanism for dilatation. We investigated if medial degeneration is specific for sporadic thoracic aortic aneurysms versus nondilated aortas. Specimens were graded by pathologists, blinded to the clinical diagnosis, according to consensus histopathological criteria. The extent of medial degeneration by qualitative (semi-quantitative) assessment was not specific for aneurysmal compared to nondilated aortas. In contrast, blinded quantitative assessment of elastin amount and medial cell number distinguished aortic aneurysms and referent specimens, albeit with marked overlap in results. Specifically, the medial fraction of elastin decreased from dilution rather than loss of protein as cross-sectional amount was maintained while the cross-sectional number, though not density, of smooth muscle cells increased in proportion to expansion of the media. Furthermore, elastic lamellae did not thin and interlamellar distance did not diminish as expected for lumen dilatation, implying a net gain of lamellar elastin and intralamellar cells or extracellular matrix during aneurysmal wall remodeling. These findings support the concepts that: (1) medial degeneration need not induce aortic aneurysms, (2) adaptive responses to altered mechanical stresses increase medial tissue, and (3) greater turnover, not loss, of mural cells and extracellular matrix associates with aortic dilatation.

scholarly journals Improved blood pressure, nitric oxide and asymmetric dimethylarginine are independent after bariatric surgery

2012 ◽  
Vol 49 (6) ◽  
pp. 589-594 ◽  
Author(s):  
R Patle ◽  
S Dubb ◽  
J Alaghband-Zadeh ◽  
R A Sherwood ◽  
F Tam ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Asymmetric Dimethylarginine ◽  
Obese Patients ◽  
Endogenous Inhibitor ◽  
Nitrite Concentration ◽  
Plasma Adma ◽  
Adma Concentration

Background Obesity is associated with hypertension, but the exact mechanism is not fully understood. Bariatric surgery significantly decreases weight and blood pressure (BP). Low plasma nitric oxide (NO) and raised asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO, concentrations are associated with both obesity and hypertension. Correlations between the changes in these parameters were studied after bariatric surgery. Methods Weight, BP, plasma ADMA and NO were measured in 29 obese patients (24 female, 5 male) before and six weeks after bariatric surgery. Results Patients were 39.2 ± 1.2 (mean ± SEM) years old and weighed 126 ± 3 kg. Six weeks after the surgery, patients had lost 10 ± 0.7 kg ( P < 0.0001) and mean arterial pressure (MAP) decreased by 11 ± 1.0 mmHg ( P < 0.0001). The plasma ADMA concentration decreased by 24 ± 2% from 5 ± 0.4 to 4.0 ± 0.3 μmol/L ( P < 0.0001). The plasma total nitrite concentration increased by 15 ± 1% from 51.4 ± 2.6 to 60 ± 3 μmol/L ( P < 0.0001). The correlation between the decrease of ADMA and increase of NO subsequent to weight loss was significant ( P < 0.0001). However, MAP was not correlated to the changes in ADMA or NO. Conclusions After bariatric surgery, beneficial changes in BP, NO and ADMA occur, but our findings suggest that these BP changes are independent of changes in the NO–ADMA axis. Other causes for the changes in BP should therefore be considered.

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