Comparison of plasma viscosity as a marker of endothelial dysfunction with nitric oxide and asymmetric dimethylarginine in subjects with dyslipidemia

2014 ◽  
Vol 57 (4) ◽  
pp. 315-323 ◽  
Author(s):  
Meltem Ercan ◽  
Sinem Firtina ◽  
Dildar Konukoglu
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Asymmetric Dimethylarginine ◽  
Plasma Viscosity

Nitric oxide and asymmetric dimethylarginine (ADMA) in malignancy associated thrombosis and their modulation by anticoagulants

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10573-10573
Author(s):  
J. Fareed ◽  
D. A. Hoppensteadt ◽  
M. Demir ◽  
O. Iqbal ◽  
W. Jeske ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Cancer Patients ◽  
Asymmetric Dimethylarginine ◽  
Oral Anticoagulants ◽  
Treated Group ◽  
Competitive Inhibitor ◽  
No Production ◽  
Open Label ◽  
Stage Renal Disease

10573 Background: Cancer associated thrombotic complications are primarily due to endothelial dysfunction and upregulation of inflammatory processes. Nitric oxide (NO) represents one of the major endothelial derived vasoactive mediators. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase which inhibits NO production at pathophysiologic levels. Plasma ADMA levels are upregulated in atherosclerosis, hypertension, end stage renal disease, chronic heart failure and microangiopathy. Methods: To test the hypothesis that endothelial dysfunction in cancer patients may result in increased ADMA levels, plasma samples were retrospectively analyzed from an open label, multidose, active comparator designed study in which all patients (n = 110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1–1.5 mg/kg sc for 5 days and further subdivided into group E which continued to receive E and warfarin (W) group which was given oral anticoagulants for a period of up to 12 weeks. Baseline blood samples (BL), 5 days post E (IPE) and 4–6 week samples from the E and W were analyzed for ADMA and NO levels by ELISA methods. Results: Both the ADMA and NO levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in the ADMA levels which persisted throughout the treatment period. However, in the W converted group the ADMA levels rebounded to an increased level indicating that E differentially regulated ADMA in these patients. The down regulation pattern of NO was similar for both E and W. Conclusions: These results suggest that patients with cancer and thrombosis exhibit simultaneous upregulation of ADMA and NO. While E and W show a differential regulation of ADMA both result in downregulation of NO. The fact that E regulates ADMA is highly suggestive of its role in iNOS regulation which may be involved in the inflammatory response in cancer patients. [Table: see text] No significant financial relationships to disclose.

Nitric oxide and asymmetric dimethylarginine and CD 40 ligand levels in malignancy associated thrombosis and their modulation by anticoagulants

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17049-17049
Author(s):  
D. Hoppensteadt ◽  
D. Fareed ◽  
O. Iqbal ◽  
A. Lale ◽  
J. Fareed
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Cancer Patients ◽  
Asymmetric Dimethylarginine ◽  
Oral Anticoagulants ◽  
Treated Group ◽  
Competitive Inhibitor ◽  
No Production ◽  
Open Label ◽  
Vasoactive Mediators

17049 Background: Cancer associated thrombotic complications are primarily due to endothelial dysfunction and upregulation of inflammatory processes. Nitric oxide (NO) represents one of the major endothelial derived vasoactive mediators. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase which inhibits NO production at pathophysiologic levels. CD 40 ligand (CD 40L) is also upregulated in cancer. Methods: To test the hypothesis that endothelial dysfunction in cancer patients may result in increased ADMA levels, plasma samples were retrospectively analyzed from an open label, multidose, active comparator designed study in which all patients (n=110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1–1.5 mg/kg sc for 5 days and further subdivided into group E which continued to receive E and warfarin (W) group which was given oral anticoagulants for a period of up to 12 weeks. Baseline blood samples (BL), 5 days post E (IPE) and 4–6 week samples from the E and W were analyzed for ADMA and CD 40L levels by ELISA methods. NO levels were measured using a chromogenic method. Results: The baseline levels of NO, ADMA and CD 40L levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in the ADMA and CD 40L levels which persisted throughout the treatment period. However, in the W converted group the ADMA and CD 40L levels rebounded to an increased level indicating that E differentially regulated ADMA in these patients. The down regulation pattern of NO was similar for both E and W. Conclusions: These results suggest that patients with cancer and thrombosis exhibit simultaneous upregulation of ADMA, CD 40L and NO. While E and W show a differential regulation of ADMA and CD 40L, both result in a downregulation of NO. The fact that E regulates ADMA is highly suggestive of its role in iNOS regulation which may be involved in the inflammatory response in cancer patients. [Table: see text] No significant financial relationships to disclose.

scholarly journals Indolent course of tubulointerstitial disease in a mouse model of subpressor, low-dose nitric oxide synthase inhibition

2008 ◽  
Vol 295 (3) ◽  
pp. F717-F725 ◽  
Author(s):  
Adelina Stoessel ◽  
Alexander Paliege ◽  
Franziska Theilig ◽  
Francesco Addabbo ◽  
Brian Ratliff ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Basement Membrane ◽  
Mouse Model ◽  
Asymmetric Dimethylarginine ◽  
In Vivo Model ◽  
No Production ◽  
Collagen Xviii

Deficiency of nitric oxide (NO) represents a consistent manifestation of endothelial dysfunction (ECD), and the accumulation of asymmetric dimethylarginine occurs early in renal disease. Here, we confirmed in vitro and in vivo the previous finding that a fragment of collagen XVIII, endostatin, was upregulated by chronic inhibition of NO production and sought to support a hypothesis that primary ECD contributes to nephrosclerosis in the absence of other profibrotic factors. To emulate more closely the indolent course of ECD, the study was expanded to an in vivo model with NG-monomethyl-l-arginine(l-NMMA; mimics effects of asymmetric dimethylarginine) administered to mice in the drinking water at subpressor doses of 0.3 and 0.8 mg/ml for 3–6 mo. This resulted in subtle but significant morphological alterations detected in kidneys of mice chronically treated with l-NMMA: 1) consistent perivascular expansion of interstitial matrix components at the inner stripe of the outer medulla and 2) collagen XVIII/endostatin abundance. Ultrastructural abnormalities were detected in l-NMMA-treated mice: 1) increased activity of the interstitial fibroblasts; 2) occasional detachment of endothelial cells from the basement membrane; 3) splitting of the vascular basement membrane; 4) focal fibrosis; and 5) accumulation of lipofuscin by interstitial fibroblasts. Preembedding labeling of microvasculature with anti-CD31 antibodies showed infiltrating leukocytes and agglomerating platelets attaching to the visibly intact or denuded capillaries. Collectively, the data indicate that the mouse model of subpressor chronic administration of l-NMMA is not a robust one (endothelial pathology visible only ultrastructurally), and yet it closely resembles the natural progression of endothelial dysfunction, microvascular abnormalities, and associated tubulointerstitial scarring.

scholarly journals The effects of renal replacement therapy on plasma, asymmetric dimethylarginine, nitric oxide and C-reactive protein levels

2008 ◽  
Vol 31 (1) ◽  
pp. 1 ◽  
Author(s):  
Halfize Uzun ◽  
Dildar Konukoglu ◽  
Mine Besler ◽  
Fusun Erdenen ◽  
Can Sezgin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Risk Factors ◽  
Renal Replacement Therapy ◽  
Endothelial Dysfunction ◽  
Replacement Therapy ◽  
Asymmetric Dimethylarginine ◽  
C Reactive Protein ◽  
Plasma Urea ◽  
Reactive Protein ◽  
Plasma Adma

Purpose: Asymmetric dimethylarginine (ADMA), nitric oxide (NOx), and C-reactive protein (CRP) are important risk factors for endothelial dysfunction and mortality in the end stage renal diseases population. The aim of the study was to investigate the relationship between renal replacement therapy and endothelial dysfunction. Methods: Plasma NOx, ADMA and CRP levels were examined in randomized selected 30 patients with chronic kidney diseases (CKD), 28 patients receiving continuous ambulatory peritoneal dialysis (PD) and 30 patients receiving regular hemodialysis (HD) and age-matched 20 healthy controls. The duration of dialysis was from 4, 5 to 11, and 6 years, respectively. Results: CKD patients had higher plasma ADMA (1.26±0.53?mol/L) and CRP levels (1.02±025mg/L) and lower NOx levels (28.6±5.4?mol/L) than controls (0.45±0.20; 0.65± 0.45; 32.5±37 respectively, P < 0.001).Plasma NOx and CRP levels were higher in HD patients (32.9±5.5?mol/L, P < 0.05 and 4.59±3.18mg/L, P < 0.001) and plasma ADMA and CRP levels were higher in PD patients (1.82±0.98?mol/L, P < 0.001 and 2.40±1.53mg/L, P < 0.001) than in CKD patients. PD patients had higher plasma ADMA levels (P < 0.05) and lower plasma NOx and CRP levels than HD patients (P < 0.001 and P < 0.001). Plasma ADMA levels were negatively correlated with NOx levels in all patient groups (P < 0.001). Plasma CRP levels in CKD and HD patients were positively correlated with plasma urea levels (r:0,437, P < 0,001) and duration of dialysis (r:0,370, P < 0.01), respectively. Conclusion: CRP and ADMA may be emerging as important risk factors for atherosclerosis in dialysis patients. Reduced NO elaboration secondary to accumulation of ADMA and elevated inflammation may be important pathogenic factors for endothelial dysfunction in both dialysis treatment strategies.

scholarly journals MARKERS OF ENDOTHELIAL DYSFUNCTION: PATHOGENETIC ROLE AND DIAGNOSTIC SIGNIFICANCE

2019 ◽  
Vol 64 (1) ◽  
pp. 34-41 ◽  
Author(s):  
T. V. Stepanova ◽  
A. N. Ivanov ◽  
N. E. Tereshkina ◽  
E. B. Popyhova ◽  
D. D. Lagutina
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Asymmetric Dimethylarginine ◽  
Vascular Endothelial ◽  
C Reactive Protein ◽  
Pathogenetic Role ◽  
Reactive Protein ◽  
Von Willebrand ◽  
Endothelial Growth Factor ◽  
Willebrand Factor

Endothelial dysfunction (ED) is considered one of the pathogenetic mechanisms of a whole range of diseases. Detection of specific biochemical markers in the blood is an effective way to ED diagnostics that characterize the vascular endothelium state. This review highlights the pathogenetic role of the factors synthesized by endotheliocytes whose level changes in biological fluids reflect violations of the endothelium basic physiological properties: vasomotor function, thromboresistance, angiogenesis regulation, barrier and adhesion functions. In particular, the participation of nitric oxide metabolites, asymmetric dimethylarginine, endothelin-1, metabolic products of arachidonic acid, von Willebrand factor, thrombomodulin, vascular endothelial growth factor, vasohibine-1 and adhesion molecules in the onset and development of ED are reviewed. The diagnostic significances of factors damaging endothelium, such as C-reactive protein, homocysteine and 8-hydroxy-2’-deoxyguanosine, are discussed. In addition, the literature data of recent years about the prospects of clinical implication the detection of the above-mentioned factors which indicates structural and functional endothelial cells damage are given. Particular attention is paid to the ED markers detection prognostic significance and the possibility of their practical use for the ED diagnosis. The search of literature for the current review was conducted in RSIC, CyberLeninka, Scopus, Web of Science, MedLine and PubMed databases from 2012 to 2018 using the following keywords: endothelial dysfunction, nitric oxide, asymmetric dimethylarginine, endothelin-1, prostacyclin, thromboxane A2, epoxyeicosatrienoic acids, von Willebrand factor, thrombomodulin, vascular endothelial growth factor, vasohibin-1, adhesive molecules, C-reactive protein, homocysteine, and 8-hydroxy-2-deoxyguanosine.

scholarly journals Uncoupling of Vascular Nitric Oxide Synthase Caused by Intermittent Hypoxia

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammad Badran ◽  
Bisher Abuyassin ◽  
Saeid Golbidi ◽  
Najib Ayas ◽  
Ismail Laher
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Intermittent Hypoxia ◽  
Asymmetric Dimethylarginine ◽  
Chronic Intermittent Hypoxia ◽  
No Production ◽  
Diabetic Mice ◽  
Enos Uncoupling ◽  
Obstructive Sleep ◽  
Oxide Synthase

Objective. Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is often present in diabetic (DB) patients. Both conditions are associated with endothelial dysfunction and cardiovascular disease. We hypothesized that diabetic endothelial dysfunction is further compromised by CIH.Methods. Adult male diabetic (BKS.Cg-Dock7m+/+Leprdb/J) (db/db) mice (10 weeks old) and their heterozygote littermates were subjected to CIH or intermittent air (IA) for 8 weeks. Mice were separated into 4 groups: IA (intermittent air nondiabetic), IH (intermittent hypoxia nondiabetic), IADB (intermittent air diabetic), and IHDB (intermittent hypoxia diabetic) groups. Endothelium-dependent and endothelium-independent relaxation and modulation by basal nitric oxide (NO) were analyzed using wire myograph. Plasma 8-isoprostane, interleukin-6 (IL-6), and asymmetric dimethylarginine (ADMA) were measured using ELISA. Uncoupling of eNOS was measured using dihydroethidium (DHE) staining.Results. Endothelium-dependent vasodilation and basal NO production were significantly impaired in the IH and IADB group compared to IA group but was more pronounced in IHDB group. Levels of 8-isoprostane, IL-6, ADMA, and eNOS uncoupling were ≈2-fold higher in IH and IADB groups and were further increased in the IHDB group.Conclusion. Endothelial dysfunction is more pronounced in diabetic mice subjected to CIH compared to diabetic or CIH mice alone. Oxidative stress, ADMA, and eNOS uncoupling were exacerbated by CIH in diabetic mice.

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

2020 ◽  
Author(s):  
Ferenc Sztanek ◽  
Hajnalka Lőrincz ◽  
Ágnes Molnár ◽  
Anita Szentpéteri ◽  
Eszter Zöld ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Diabetic Neuropathy ◽  
Asymmetric Dimethylarginine ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Tnf Α ◽  
Type 2 Diabetic

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 < 0.001), as well as TNF-α concentrations (1.21 ±0.42 pg/ml vs. 1.05 ±0.5 pg/ml, p < 0.05), while NO levels were significantly increased (16.78 ±11.1 vs. 21.58 ±8.84 µmol/l, p < 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 < 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.

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