Plasma Endothelin-1 Levels Research Articles

Subclinical sleep apnoea and plasma levels of endothelin-1 among young and healthy adults

ObjectiveObstructive sleep apnoea (OSA) is a risk factor for vascular disease and other adverse outcomes. These associations may be at least partly due to early endothelin-1 (ET-1)-mediated endothelial dysfunction (ED)....

Plasma levels of endothelin-1 and renal function among young and healthy adults.

Endothelin-1 (ET-1), a vasoconstrictive and pro-inflammatory peptide, is associated with several cardiovascular risk factors and outcomes. We aimed to investigate the association of plasma ET-1 levels and renal function among young and healthy adults. Individuals aged 25-41 years were enrolled in a population-based cohort study. Main exclusion criteria were established kidney disease, cardiovascular diseases, diabetes mellitus and a body mass index>35 kg/m2. Fasting venous plasma samples were used to measure creatinine, cystatin C and ET-1. The estimated glomerular filtration rate (eGFR) was calculated using the creatinine based chronic kidney disease epidemiology collaboration (CKD-EPI) formula. Multivariable regression models were constructed to assess interrelationships of plasma ET-1 with parameters of renal function. Median age of the 2139 participants was 37 years, 47% males. Median creatinine and eGFR were 67 μmol/L and 112 mL/min/1.73 m2, respectively. Using quartile one as the reference group, the β-coefficients (95% confidence intervals [CIs]) for eGFR were 0.06 (- 1.22 to 1.35),-0.66 (- 1.95 to 0.62) and-1.70 (- 3.01 to-0.39) for quartiles 2-4 (p-for-trend=0.0056), respectively and β-coefficients (95% CIs) for cystatin C were 0.002 (- 0.01 to 0.02), 0.02 (0.003-0.03) and 0.03 (0.01-0.04) for quartiles 2-4 (p-for-trend<0.0001), respectively. Using ET-1 as a continuous variable, the β-coefficient (95% CI) for eGFR per 1-unit increase was-1.82 (- 3.19 to-0.44, p=0.0095) and 0.02 (0.01-0.04, p=0.0003) for cystatin C. Similar results were found between creatinine and ET-1 levels. ET-1 levels are strongly associated with parameters of renal function among young and healthy adults, suggesting an important role of ET-1 and endothelial function in the regulation of kidney function.

Plasma endothelin-1 levels in patients with resistant hypertension: effects of renal sympathetic denervation

Introduction: Resistant arterial hypertension (RHT) is defined as poor controlled blood pressure (BP) despite optimal doses of three or more antihypertensive agents, including a diuretic. In the development of RHT, hyperactivity of sympathetic (SNS) and renin–angiotensin–aldosterone (SRAA) systems are involved, and SNS is a potent stimulator of vasoactive endothelin-1 (ET-1) peptide. Renal sympathetic denervation (RSD) through disrupting renal afferent and efferent nerves attenuates SNS activity.Material and methods: We carried out pilot study investigating the effect of RSD on BP and plasma ET-1 levels in consecutive 9 RHT patients (7 male and 2 female, mean age of 56 ± 13.3).Results: After 12 months of the RSD, we observed a significant reduction of BP office, 24-h ambulatory BP monitoring (ABPM) (p < 0.05, respectively), and “non-dipping” pattern (from 55% to 35%) (p < 0.05). Moreover, RSD significantly decreased plasma ET-1 levels in both renal artery (at right from 21.8 ± 4.1 to 16.8 ± 2.9 pg/ml; p = 0.004; at left from 22.1 ± 3.7 to 18.9 ± 3.3 pg/ml; p = 0.02). We observed positive correlations between plasma renal arteries ET-1 levels and systolic BP values at ABPM [Global-SBP (r = 0.58; p < 0.01), Diurnal-SBP (r = 0.51; p < 0.03) and Nocturnal-SBP (r = 0.58; p < 0.01), respectively].Discussion: Our data confirmed the positive effects of RSD on BP values in patients with RHT, and showed a possible physio-pathological role of ET-1.KEY MESSAGESRSD is associated to a significant reduction of plasma ET-1 levels, representing an useful tool into reduction of BP in RHT patients.

ENDOTHELIAL DYSFUNCTIONS AND THEIR CORRECTION IN WOMEN WITH EARLY POSTMENOPAUSE

Aim. To evaluate the nature of the dysfunction of the endothelium in postmenopausal women with climacteric syndrome, peculiarities of its changes during long-term use of a fixed low-dose combination of 17β-estradiol 1 mg/drosperidone 2 mg daily (Е2 1 mg/DRSP 2 mg). Material and methods. A non-randomized, uncontrolled study included 162 women in early postmenopausal period with climacteric syndrome. Patients were divided into 2 groups. Patients of the main group (n=84) received menopausal hormone therapy (MHT) with the fixed combination of Е2 1 mg/DRSP 2 mg. Patients of the control group (n=78) did not receive MHT. The duration of the follow-up was 5.2 years. The endothelium dependent vasodilation (EDVD) of brachial artery was assessed by reactive hyperemia. Endothelial dysfunction (ED) markers - plasma levels of endothelin-1 (ET-1), NO metabolites, asymmetric dimethylarginine (ADMA) and von Willebrand factor antigen (vWF:Ag) - were studied by a highly sensitive quantitative enzyme-linked immunosorbent assay. Results. The examined postmenopausal women with climacteric syndrome had significant increase in the concentration of ET-1 up to 1.0 (0.7-1.3) fmol/ml, increased levels of vWF:Ag up to 0.835 (0.760-0.990) U/ml and reduction in the level of the total content of stable metabolites of nitric oxide (NOx) to 39.2 (35.4-43.7) μmol/l. Disorders of EDVD of the brachial artery were observed in 50 (59.5%) women of the main group and in 45 (57.6%) women of the control group (p=0.7). The relationships between EDVD parameters and levels of ADMA (r=-0.31, p=0.029) and NOx (r=0.31, p=0.002) were revealed. In patients with impaired EDVD, a significant decrease in the level of stable NO metabolites and an increase in ADMA and ET-1 levels were detected. A significant increase in the EDVD of the brachial artery was observed throughout the follow-up period. Besides an increase in NO metabolites level, and decrease in the ET-1 and ADMA levels were found by the 12th month of MHT. Conclusions. Disorders of endothelial function were found in the majority of women in early postmenopausal period, the most marked changes were in patients with impaired vasoreactivity of brachial artery. Favorable changes in vascular endothelium function were observed during long-term MHT with the fixed combination of Е2 1 mg/DRSP 2 mg.

MODERN APPROACH TO ASSESS THE ASTHMA CONTROL AND TREATMENT EFFICASY IN DIFFERENT PHENOTYPES BY ENDOTHELIAN DISFUNCTION

The aim of this study is to measure the level of the endothelin-1 in blood samples and to assess vasoactive function of the endothelial in asthma patients with different phenotypes and to develop the methods of the objective assess of the ongoing treatment. Materials and methods. 119 asthma patients were separated into several phenotypes: patients with atopic asthma (60 pat); patients with ACOS (35 pat); asthma with obesity (24 pat). In all patients endothelium-dependent vasodilation and plasma level of endothelin-1 were assessed. Results. Endothelial dysfunction revealed in all asthma phenotypes. The highest level of the endothelin-1 shown in ACOS patients. In patients which achieved asthma control during three month of the anti-inflammatory therapy showed decreasing of the endothelin-1 level by 1,5 times in comparison with basic level (0,35 ± 0,06 fmol/ml and 0,64 ± 0,15 fmol/ml respectively, р < 0,01). But in patients with persistent symptoms and/or without lung function improvement the level of the endothelin-1 was not decreased significantly. Conclusions. Change of the functional conditions of the endothelial depend on the time and severity and phenotype of the asthma. The endothelin-1 level and the endothelium-dependent vasodilatation assess on the course of the treatment allow to reveal success of this anti- inflammatory therapy.

Does sleep quality affects the immediate clinical outcome in patients undergoing coronary artery bypass grafting: A clinico-biochemical correlation.

Objective:Poor sleep quality is emerging as high prevalence among the patients suffering from cardiometabolic disturbances. The vascular polypeptide endothelin 1 (ET-1) is involved in many of the health disorders. However, its potential involvement in patients having poor sleep quality along with cardiovascular problem is limited. The present study was formulated to conduct a prospective analysis of the relationship between ET-1 and in hospital outcome in sleep disorder patients undergoing routine coronary artery bypass grafting (CABG).Methods:A total of 156 patients were enrolled and divided into two groups based on the Pittsburg Sleep Quality Index (PSQI) of ≤5 (Group I, n = 101) or >5 (Group II, n = 55). Blood sample was collected before anesthesia induction (ET-1a) and at 48 h (ET-1b) to analyze the plasma ET-1 and blood sugar level. The patients were monitored for any intraoperative adverse events and postoperative complications during their hospital stay.Results:Both groups were comparable in relation to age, sex, incidence of smoking and alcohol consumption. The distribution of comorbid conditions was also similar in both groups. The ET-1 level was higher in Group II than Group I before anesthesia induction as well as 48 h postoperatively (4.5 ± 1.75 vs. 10.61 ± 9.3, P = 0.001; 2.08 ± 1.3 vs. 8.3 ± 9.86, P = 0.0001, respectively). The Group II patients had a longer duration of mechanical ventilation (14.6 ± 12.05 vs. 10.1 ± 8.19, P = 0.001), Intensive Care Unit stay (2.08 ± 0.95 vs. 2.7 ± 1.45, P = 0016) and hospital stay (5.98 ± 1.73 vs. 7.8 ± 3.66, P = 0.0001, respectively). The high number of patients from Group II required inotrope and intra-aortic balloon pump support while compared with Group I (P ≤ 0.05 in each). The overall postoperative complication rate was significantly higher among patients with PSQI of >5 (Group II) except the rate of infection and neurological complications which was similar among both group of patients. The postoperative in hospital mortality was nil in Group I and 3.6% in Group II (P = 0.05). There was a strong relationship between PSQI and ET-1 at both the time points.Conclusion:Poor sleep quality associated with a higher incidence of adverse perioperative events in patients undergoing elective CABG. There exists a potential link between poor sleep quality and ET-1 in these groups of patients.

Neurohumoral and Endothelial Responses to Heated Water-Based Exercise in Resistant Hypertensive Patients.

The neurohumoral and endothelial responses to the blood pressure (BP) lowering effects of heated water-based exercise (HEx) in resistant hypertension (HT) patients remain undefined.Methods and Results:We investigated these in 44 true resistant HT patients (age 53.3±0.9 years, mean±SEM). They were randomized and allocated to 2 groups, 28 to a HEx training protocol, which consisted of callisthenic exercises and walking in a heated pool for 1 h, three times weekly for 12 weeks and 16 patients to a control group maintaining their habitual activities. Measurements made before and after 12 weeks of HEx included clinic and 24-h BP, plasma levels of nitric oxide, endothelin-1, aldosterone, renin, norepinephrine and epinephrine, as well as peak V̇O2, and endothelial function (reactive hyperemia). After 12 weeks of HEx patients showed a significant decrease in clinic and 24-h systolic and diastolic BPs. Concomitantly, nitric oxide increased significantly (from 25±8 to 75±24 μmol/L, P<0.01), while endothelin-1 (from 41±5 to 26±3 pg/mL), renin (from 35±4 to 3.4±1 ng/mL/h), and norepinephrine (from 720±54 to 306±35 pg/mL) decreased significantly (P<0.01). Plasma aldosterone also tended to decrease, although not significantly (from 101±9 to 76±4 pg/mL, P=NS). Peak V̇O2increased significantly after HEx (P<0.01), while endothelial function was unchanged. No significant change was detected in the control group. The BP-lowering effects of HEx in resistant HT patients were accompanied by a significant reduction in the marked neurohumoral activation characterizing this clinical condition.

Activation of the Mineralocorticoid Receptor Stimulates Protein Disulfide Isomerase: Role in Sickle Cell Disease

Activation of the mineralocorticoid receptor (MR), a critical component of the Renin-Angiotensin-Aldosterone (ALDO)-System (RAAS), has been shown to play an important role in inflammatory and vascular endothelial responses in addition to its well-described effects on sodium and water homeostasis. Activationof endothelial cells leads to, among other factors, increased endothelin-1 (ET-1) and protein disulfide isomerase (PDI) release. PDI and ET-1 contribute to vascular inflammation and are increased in patients with SCD and sickle transgenic mouse models. The MR is a member of the steroid family of nuclear receptors and transcription factors that upon activation binds to hormone response elements of edn1, the gene for ET-1, leading to increased ET-1 expression.In vivo, blockade of MR has been shown to reduce circulating ET-1 levels and ET-1 mRNA expression. However, the role of MR in SCD is unclear. We hypothesized that MR blockade in sickle transgenic mice would reduce PDI activity and improve hematological parameters and inflammation. We first studied EA.hy926 (EA) cells, a human endothelial cell line that expresses MR. We incubated EA cells with ALDO (10-8 M), an MR agonist, for 24 hr and observed a rise in PDI mRNA levels by qRT-PCR (P<0.01, n=5), an event that was blocked by pre-incubation of EA cells with 1 μM canrenoic acid (CA), an MR antagonist (P<0.05, n=5). We then measured PDI activity in the supernatant of ALDO-stimulated EA cells using a Di-E-GSSH fluorescent marker and observed a rise in PDI activity following ALDO (10-8 M) when compared to vehicle treatment (P<0.05; n=5). To test the in vivo effects of MR activation, we studied Berkeley Sickle Transgenic (BERK) mice that were randomized to receive either normal rodent chow or chow containing eplerenone (156 mg/kg per day), an MR antagonist (MRA), for 14 days. We observed significantly lower plasma PDI activity in mice treated with MRA than those on regular chow (63.7 ± 8.7 control diet to 47.9 ± 2.4 eplerenone, Relative Fluorescence Units (RFU); P<0.005, n=6 and 9, respectively). Treatment with MRA was associated with reduced plasma ET-1 and myeloperoxidase (MPO) levels in BERK mice. We also studied RBC Gardos channel activity in these mice and observed a significant reduction in clotrimazole-sensitive K+ efflux following MR blockade (2.49±0.5 control and 1.37±0.3 mmol/1013 cells x hr; P<0.04 n= 5 and 7 respectively). Consistent with these results, MR blockade was associated with increases in both erythrocyte MCV (41.3±2.5 vs 47.4±1.1 fL, P<0.03, n=7) and reticulocyte MCV (53.6.3±2.8 vs 60.1±0.6 fL, P<0.02, n=7). We also studied gene expression by qRT-PCR in heart tissue from these mice and observed that MR blockade reduced mRNA expression of: ET-1 (0.654 ± 0.233, P<0.05, n=5 and n=7); PDI (0.546 ± 0.063, P<0.01, n=5 and n=7); and Tumor Necrosis Factor Receptor Superfamily Member 1A mRNA (0.464 ± 0.061, P<0.01, n=5 and n=7). Thus, our results suggest a novel role for RAAS and, in particular, MR activation in SCD. DisclosuresNo relevant conflicts of interest to declare.

The impact of different doses of atorvastatin on plasma endothelin and platelet function in acute ST-segment elevation myocardial infarction after emergency percutaneous coronary intervention

Objective: To investigate the effects of different doses of atorvastatin on plasma endothelin and platelet function in acute ST-segment elevation myocardial infarction (STEMI) patients after emergency percutaneous coronary intervention(PCI). Methods: A total of 120 patients with acute STEMI treated with emergency PCI were enrolled and randomly divided into 20 mg of atorvastatin treatment group (standard group, n=60), and 40 mg of atorvastatin treatment group (intensive group, n=60). The blood C reactive protein (CRP), blood lipid profiles, plasma endothelin (ET) were measured before atorvastatin treatment and after 7 days of treatment, respectively. The platelet fibrin clot strength induced by ADP (MAADP) was determined by thrombelastography(TEG). Results: Seven days after of atorvastatin treatment, the level of plasma ET in intensive group was significantly lower than that in standard group [(0.49±0.21)pmol/L vs (0.63±0.58)pmol/L, P<0.05]. Moreover, the MAADP in intensive group was significantly decreased compared with the standard group [(38.4±17.4) mm vs (45.7±14.5) mm, P<0.05]. There was a positive correlation between the ET level and MAADP in intensive group after treatment (r=0.378, P<0.05). However, no significantly differences could be viewed in the CRP and LDL-C levels between the two groups (P>0.05). Conclusion: In patients with acute STEMI, early administration of 40 mg atorvastatin after emergency PCI could significantly reduce the vascular endothelial injury, improve endothelial function, and reduce the residual platelet activity.

Pharmacodynamic action and mechanism of Du Liang soft capsule, a traditional Chinese medicine capsule, on treating nitroglycerin-induced migraine

Ethnopharmacological relevanceDu Liang soft capsule (DL) is a traditional Chinese medicine for treating migraines; it is made from two Chinese herbs, including LigusticumstriatumDC., root; Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., root. Aim of the studyIn the present study, we aimed to elucidate the pharmacodynamic action of DL and its mechanism in an animal model of migraines induced by glyceryl trinitrate (GTN). Materials and methodsSixty rats were randomly divided into six groups, including a normal control group, model control group, positive group (Sumatriptan 0.006gkg−1), and three DL groups (0.44, 1.31 and 3.93gkg−1). All rats were intragastrically treated with the corresponding treatment for 7 consecutive days, and they were subcutaneously injected with GTN (10mgkg−1) 30min after the last treatment, except in the normal control group. After model establishment, the behaviors of all rats, including head scratching, cage climbing, and the development of red ears were observed continuously by digital camera every 30min for 3h. Four hours after GTN treatment, all rats were anaesthetized and the blood and tissue samples were collected. Plasma calcitonin gene related to peptide (CGRP) and endothelin (ET) levels were measured using the radioimmunoassay method, and serum NO was determined by the colorimetric method. Afterwards, the brainstem tissues were dissected and washed with physiological saline, and divided evenly into two parts. One part was used to test the monoamine levels, including levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA), by the fluorometric method, and the other part was used to determine the nuclear factor kappaB (NF-κB) p65, nuclear c-fos, inducible nitric oxide synthase (iNOS), interleukin (IL)-1β (IL-1β), and cyclooxygenase-2 (COX-2) levels by Western blot analysis. ResultsIn the pharmacodynamic action assay, DL (1.31 and 3.93gkg−1) greatly improved the abnormal behaviors of migraine rats, including head scratching and cage climbing, and the development of red ears. In the mechanism assay, compared with the control group, the plasma CGRP and serum NO levels and the brainstem 5-HT, NE and DA levels in the DL administration groups were significantly decreased; and the plasma ET levels were remarkably increased. Moreover, down-regulation of NF-κB p65, c-fos and pro-inflammatory cytokines, including iNOS, IL-1β and COX-2 in the brainstem in the DL administration groups were observed by Western blot analysis. ConclusionsThe above results suggested that DL has a therapeutic effect on migraines, and its mechanism may be related to adjusting the level of neurotransmitters and vasoactive substances, consequently relieving neurogenic inflammation.

Analysis on mechanism of ATP-sensitive K+ channel opener natakalim improving congestive heart failure after myocardial infarction.

The action mechanism of natakalim, a novel ATP-sensitive potassium channel opener, was studied in ameliorating the congestive heart failure (CHF) after myocardial infarction. A total of 25 healthy Wistar male rats (age, 10 weeks; average weight, 300 g) were selected, and the CHF models after acute myocardial infarction (AMI) were prepared by ligation of left anterior descending branch. They were randomly divided into the sham operation group, the model group and the groups of 1, 3 and 9 mg/kg/day natakalims. Each group had 5 mice that were sacrificed after 8 weeks. We compared left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), left ventricular mass index, myocardial cell cross-sectional area, myocardial collagen content, plasma endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) levels. Compared with the sham operation, the LVEDD and NT-proBNP in the model group and each natakalim group were elevated. LVEF decreased significantly, while the left ventricular mass index, myocardial cell cross-sectional area, myocardial collagen content, plasma ET-1 and eNOS levels increased. Natakalim intervention improved the above changes and the improvement effect of 3 mg/kg/day group was the highest. The mechanism of natakalim against the endothelin system can be explained by the fact that inhibiting ET-1 synthesis can reduce the ET-1 levels in circulation leading to the release of NO and PGI2. Inhibition of the vasoconstriction effect of ET-1 can improve the hemodynamics of high-load status and ameliorate the cardiac systolic and diastolic functions. In conclusion, natakalim can improve the ventricular remodeling of CHF after AMI, and 3 mg/kg/day was the most effective dose.

Activated Transcription Factor 3 in Association with Histone Deacetylase 6 Negatively Regulates MicroRNA 199a2 Transcription by Chromatin Remodeling and Reduces Endothelin-1 Expression

Previous studies showed that high levels of placenta growth factor (PlGF) correlated with increased plasma levels of endothelin-1 (ET-1), a potent vasoconstrictor, in sickle cell disease (SCD). PlGF-mediated transcription of the ET-1 gene occurs by activation of hypoxia inducible factor 1α (HIF-1α) and posttranscriptionally by microRNA 199a2 (miR-199a2), which targets the 3' untranslated region (UTR) of HIF-1α mRNA. However, relatively less is known about how PlGF represses the expression of miR-199a2 located in the DNM3 opposite strand (DNM3os) transcription unit. Here, we show that PlGF induces the expression of activated transcription factor 3 (ATF3), which, in association with accessory proteins (c-Jun dimerization protein 2 [JDP2], ATF2, and histone deacetylase 6 [HDAC6]), as determined by proteomic analysis, binds to the DNM3os promoter. Furthermore, we show that association of HDAC6 with ATF3 at its binding site in this promoter was correlated with repression of miR-199a2 transcription, as shown by DNM3os transcription reporter and chromatin immunoprecipitation (ChIP) assays. Tubacin, an inhibitor of HDAC6, antagonized PlGF-mediated repression of DNM3os/pre-miR-199a2 transcription with a concomitant reduction in ET-1 levels in cultured endothelial cells. Analysis of lung tissues from Berkeley sickle (BK-SS) mice showed increased levels of ATF3 and increased expression of ET-1. Delivery of tubacin to BK-SS mice significantly attenuated plasma ET-1 and PlGF levels. Our studies demonstrated that ATF3 in conjunction with HDAC6 acts as a transcriptional repressor of the DNM3os/miR-199a2 locus.

Proteinase activated receptor-2 counterbalances the vascular effects of endothelin-1 in fibrotic tight-skin mice.

The majority of the severe vascular complications in fibrosis are a consequence of a deregulated activity of mediators controlling vasomotor tone. One of the most important of these mediators is endothelin-1 (ET-1). Here, we have investigated the role of proteinase-activated receptor 2 (PAR2) in the vascular dysfunction in a model of fibrosis, using tight-skin (Tsk) mice. Aortas were collected from Tsk, transgenic over-expressing PAR2 (TgPAR2), PAR2 deficient (PAR2-/- ) or the corresponding WT mice. Histological and immunohistochemistry analysis for α-smooth muscle actin, PAR2 and ET-1 receptors were performed on aorta sections. Vascular responses to phenylephrine, ET-1 and PAR2 activating peptide (PAR2-AP) were assessed on aortic rings. In aortas from Tsk mice, responses to phenylephrine were reduced, contractions to ET-1 were increased and vasorelaxation to PAR2-AP was enhanced. These alterations matched changes observed in whole vessel architecture such as vascular fibre re-organization, increased collagen deposition and enhanced α-smooth muscle actin expression. Expression of both ETA receptors and PAR2 was enhanced in Tsk mice. Antagonism of PAR2 potentiated vascular effects of ET-1, whereas antagonism of ETA receptors increased vasorelaxation induced by PAR2-AP. In TgPAR2 mice, responses to ET-1 and ET-1 plasma levels were reduced. Conversely, PAR2-/- mice showed enhanced ET-1 induced contraction in aortic rings and higher circulating ET-1 levels. Our data show that PAR2 counterbalanced enhanced contractions to ET-1 in aortas from Tsk mice. PAR2 could represent a possible target for novel drugs in the treatment of vascular complications in fibrosis. This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.

GW27-e0526 Plasma level of big endothelin-1 in patients with hypertrophic cardiomyopathy

GW27-e0526 Plasma level of big endothelin-1 in patients with hypertrophic cardiomyopathy

GW27-e1105 Endothelin-1 in Left Stellate Ganglion Promotes Post-infarction Ventricular Arrhythmias by Increasing Cardiac Sympathetic Activity

Paraventricular Nucleus (PVN) and Left stellate ganglion (LSG) are important central and peripheral components of cardiac sympathetic afferent reflex (CSAR) respectively. Studies have shown that endothelin-1 (ET-1) in PVN could increase sympathetic activity and elevated plasma level of ET-1 was

Antioxidant Response of Chronic Wounds to Hyperbaric Oxygen Therapy.

We analyzed the effects of the clinical hyperbaric oxygen therapy (HBOT) on the plasma antioxidant response and levels of endothelin-1, Interleukine-6 (IL-6) and vascular endothelial growth factor (VEGF) in patients with chronic wounds (20.2±10.0 months without healing). They received 20 HBOT sessions (five sessions/week), and blood samples were obtained at sessions 1, 5 and 20 before and 2 hours after the HBOT. An additional blood sample was collected 1 month after wound recovery. Serum creatine kinase activity decreased progressively in accordance with the wound healing. Plasma catalase activity significantly increased after the first and fifth sessions of HBOT. Plasma myeloperoxidase activity reported significantly lower values after sessions. Plasma VEGF and IL-6 increased after sessions. Endothelin-1 levels were progressively decreasing during the HBOT, being significant at the session 20. Plasma malondialdehyde concentration was significantly reduced at the last session. Both creatine kinase activity and malondialdehyde levels were maintained lower 1 month after wound recovery respect to initial values. In conclusion, HBOT enhanced the plasma antioxidant defenses and may contribute to activate the healing resolution, angiogenesis and vascular tone regulation by increasing the VEGF and IL-6 release and the endothelin-1 decrease, which may be significant factors in stimulating wound healing.

Correlation between plasma NGAL and ET-1 levels and cognitive dysfunction in patients with chronic obstructive pulmonary disease

Objective To investigate the relationship between the plasma neutrophil gelatinase-associated lipocalin (NGAL)and endothelin-1 (ET-1) levels and cognitive dysfunction in chronic obstructive pulmonary disease (COPD) patients. Methods A case-control study was performed, consisting of 128 patients with COPD(68 patients without cognitive dysfunction and 60 patients with cognitive dysfunction) and 70 normal controls .All patients with COPD were diagnosed by pulmonary function tests and plasma levels of NGAL and ET-1 were determined by enzyme immunoassay.The cognitive function was evaluated by the MMSE and MoCA. Results ①Compared with normal control, the levels of plasma NGAL and ET-1 were increased(NGAL: (2.20±0.60)μg/L vs (1.69±0.73)μg/L, P<0.05; ET-1: (26.19±10.55)pg/ml vs (13.05±2.37)pg/ml, P<0.05) in COPD patients without cognitive dysfunction and in COPD patients with cognitive dysfunction(NGAL: (3.80±2.75)μg/L vs (1.69±0.73)μg/L, P<0.01; ET-1: (37.82±0.29)pg/ml vs (13.05±2.37)pg/ml, P<0.01). Compared with the COPD patients without cognitive dysfunction, the levels of plasma NGAL and ET-1 were also increased in COPD patients with cognitive dysfunction(all P<0.05). ②The plasma NGAL levels were correlated negatively with MMSE scores(r=-0.524, P<0.05), and negatively correlated with MoCA scores (r=-0.527, P<0.05). The plasma ET-1 levels were negatively correlated with MMSE scores( r=-0.549, P<0.05), and negatively correlated with MoCA scores(r=-0.558, P<0.05). The levels of NGAL and ET-1 were positively correlated(r=0.564, P<0.05). Conclusion NGAL and ET-1 may be involved in the pathophysiological process of cognitive dysfunction in patients with COPD, which provides a certain clinical value for the assessment of cognitive dysfunction in patients with COPD. Key words: Chronic obstructive pulmonary disease; Cognitive dysfunction; Neutrophil gelatinase-associated lipocalin; Endothelin-1

PP.14.03] PLASMA MARKERS OF ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH HYPERTENSION AND ATRIAL FIBRILLATION

Objective: To evaluate plasma markers of endothelial dysfunction in patients with hypertension and different categories of atrial fibrillation (AF). Design and method: The study included 113 hypertensive patients aged 34 to 72 years (mean age 60.2 ± 5.7 years). Based on AF category, patients were divided into 3 groups: the first group consisted of 50 patients with paroxysmal AF; 33 patients with permanent AF were included into the second group, and 30 patients in sinus rhythm were designated as the control group. The plasma collagen-binding activity of von Willebrand factor (vWf) and endothelin-1 (ET-1) level were measured in all the patients. Results: Collagen–binding activity vWf was significantly higher in patients with hypertension and permanent AF (150 IU/dl, p < 0.05) in comparison with the patients with paroxysmal AF (106 ± 12 IU/dl, p = 0.04) and the controls (84 ± 11 IU/dl, p = 0.001). There was a significant direct correlation between AF paroxysm frequency per year and collagen-binding activity of vWf in hypertensive patients with paroxysmal AF (r = 0.59041). No significant differences in the average ET-1 levels were observed between the patients with AF and hypertensives in sinus rhythm. The plasma ET-1 level was directly associated with the grade of hypertension in all the groups. Conclusions: Collagen–binding activity of vWf did not correlate with the grade of hypertension and was significantly higher in patients with permanent AF when compared with the control group subjects. There was a significant direct correlation between AF paroxysm frequency and collagen-binding activity of vWf in patients with paroxysmal AF. Plasma endothelin-1 level was directly associated with the grade of hypertension in both AF patients and the control subjects in sinus rhythm. No correlation between ET-1 level and AF category was found.

Suppressed endothelin-1 by anti-VEGF therapy is important for patients with BRVO-related macular edema to improve their vision.

BackgroundBranch retinal vein occlusion (BRVO) commonly occurs at the arteriovenous crossing in the unilateral eye, and cardiovascular diseases can be risk factors of BRVO. However, the pathomechanism leading to BRVO is not yet clear. In addition to mechanical compression, the vein might locally constrict due to an altered biochemical environment, such as an increase in the concentration of endothelin-1 (ET-1). We evaluated changes in ET-1 following injection of intravitreal bevacizumab (IVB), which is the anti-vascular endothelial growth factor (VEGF) agent with the longest serum half-life, to determine the effect on BRVO-related macular edema.MethodsTwenty consecutive patients with BRVO-related macular edema (10 males, 10 females; age range 56–83 years) who visited our hospital were included in this prospective study. Visual acuity (VA); central retinal thickness (CRT), determined by macular optical coherence tomography (OCT); and plasma ET-1 levels were obtained before IVB treatment and 1 month later.ResultsPatients had hypertension (80 %), dyslipidemia (50 %), diabetes mellitus (35 %), or collagen disease (5 %). Mean CRT was significantly decreased from 673.0 ± 327.8 to 388.2 ± 155.0 μm (P = 0.0007), and mean VA was significantly improved after IVB (P = 0.0239). Mean plasma ET-1 was significantly decreased from 1.272 ± 0.451 to 1.095 ± 0.316 pg/mL (P = 0.0238); however, the plasma ET-1 level was increased in all five patients who did not show improved VA after IVB.ConclusionsIn patients with BRVO-related macular edema, anti-VEGF therapy leads to an expected reduction in ET-1 levels; however, the ET-1 level was found to increase in some patients; this is clearly related to less improvement of VA after anti-VEGF therapy.Trial registrationUniversity hospital Medical Information Network (UMIN) Center UMIN000013236. Registered 10 October, 2012.

Endothelin-1 Gene Polymorphism and Its Level Predict the Risk of Venous Thromboembolism in Male Indian Population.

Genes related to endothelial function are responsible for the regulation of vascular functions. The aim of this study is to investigate whether endothelial gene-associated polymorphism and their plasma levels can be used to predict the risk for venous thromboembolism (VTE). We studied 133 patients with VTE and 164 healthy controls. Endothelin (EDN) G8002A, EDN T1370G, EDN 3A/4A, eNOSG894T, angiotensin-converting enzyme I/D, vascular endothelial growth factor C936T, and endothelial cell protein C receptor A6936G polymorphism was genotyped by restriction fragment length polymorphism. Plasma levels of endothelin 1 (EDN1), endothelial nitric oxide synthase, and angiotensin-converting enzyme were measured by enzyme-linked immunoassay kit. The genotype and allele frequency between control and patients with VTE were significantly altered only for EDN T1370G polymorphism. The plasma EDN1 concentration was relatively higher in patients with VTE ( P = .0017) compared to healthy controls and showed an association with the EDN1 gene polymorphism in male Indian population. Logistic regression model analysis for EDN T1370G indicated a significant association between EDN G allele and occurrence of VTE. The EDN1 gene polymorphism may play a significant role in predicting individual's susceptibility toward VTE and its clinical progression.