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Objects The aim of this trial was to evaluate the effect of short-term high-dose atorvastatin therapy on levels of high-sensitivity C-reactive protein (hs-CRP), malonaldehyde (MDA), endothelin-1(ET-1), matrix metalloproteinases (MMPs), and left ventricular (LV) remodeling in patients with first time attack of acute anterior myocardial infarction (AAMI) .Methods A hundred and three patients with first time attack of AAMI who underwent successful primary percutaneous coronary intervention were randomized to receive atorvastatin 40 mg once daily for 1 week followed by 20 mg once daily (intensive treatment group, IT group, n=49), or atorvastatin 20 mg once daily (standard treatment group, ST group, n=54). Plasma levels of hs-CRP, MDA, ET-1, MMP-2 and MMP-9 were measured on admission, at 1 week, 2 weeks and 6 months follow up and compared between the IT group and ST group. Echocardiography was performed on admission, at 2 week, and 1 year follow up. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were measured at each echocardiographic examination and compared between the IT group and ST group.Results Plasma levels of hs-CRP (F=7.718, P=0.009), ET-1 (F=7.882, P=0.006), MMP-9 (F=4.834, P=0.028) and pro-BNP (F=4.603, P=0.032) were significantly lower at 1 week after initial onset of AAMI in the IT group compared with the ST group. The changes of LVEDV, LVESV, and LVEF at the 1 year follow-up from the admission did not differ between the IT group and the ST group (t=0.722, P=0.444; t=1.228, P=0.221; t=1.354, P=0.187, repectively).Conclusions Short-term high-dose atorvastatin treatment for AAMI was associated with lower hs-CRP, ET-1 and MMP-9 levels compared to the standard dose treatment. However, this beneficial effect is not likely to related to the left ventricular remodeling.

Arterial compliance (AC) is an index of the elasticity of large arteries. Endothelial dysfunction has been reported to result in reduced arterial compliance, which represents increased arterial stiffness. A reduction in AC is elicited by high-intensity resistance training, however the mechanisms are obscure. Because a single bout of resistance exercise causes a transient increase in circulating plasma endothelin-1 in humans, some vasoconstrictors may play a role in the mechanisms. The present study aimed to investigate whether resistance training-induced decrease in AC is associated with changes in circulating vasoconstrictors levels in young men. Young sedentary men were assigned to control (n=5) or training (n=9) groups. The training group performed four-week high-intensity resistance training (weight training exercise; three sessions/week). We measured AC and plasma levels of endothelin-1, angiotensin II, and norepinephrine before and after intervention. Resistance training significantly decreased AC, whereas the changes in plasma levels of neither endothelin-1, nor angiotensin II, nor norepinephrine were significantly different between the control and the training groups. Moreover, we found no significant correlations between changes in circulating plasma levels (endothelin-1, angiotensin II, and norepinephrine) and in the AC. Despite of no alteration of the resting circulating plasma levels (endothelin-1, etc.), we cannot exclude a possibility that the tissue/local concentrations of vasoconstrictors (endothelin-1, etc.) around the vessels might be increased and also involved in a reduction of AC in the training group. Taken together, the present results suggest that circulating vasoconstrictors (endothelin-1, etc.) in plasma are not involved in a reduction in AC by the resistance training.

Pulmonary arterial hypertension (PAH) is a chronic progressive disease which leads to elevated pulmonary arterial pressure and right heart failure. 3,7-Bis(2-hydroxyethyl)icaritin (ICT), an icariin derivatives, was reported to have potent inhibitory activity on phosphodiesterase type 5 (PDE5) which plays a crucial role in the pathogenesis of PAH. The present study was designed to investigate the effects of ICT on monocrotaline (MCT)-induced PAH rat model and reveal the underlying mechanism. MCT-induced PAH rat models were established with intragastric administration of ICT (10, 20, 40 mg/kg/d), Icariin (ICA) (40 mg/kg/d) and Sildenafil (25 mg/kg/d). The mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. Pulmonary artery remodeling was assessed by H&E staining. Blood and lung tissue were collected to evaluate the level of endothelin 1 (ET-1), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The expressions endothelial nitric oxide synthase (eNOS) and PDE5A in lung tissues were determined by Western blot analysis. The results showed that ICT reduced RVHI and mPAP, and reversed lung vascular remodeling in rats with MCT-induced PAH. ICT also reversed MCT-induced ET-1 elevation, NO and cGMP reduction in serum or lung tissue. Moreover, ICT administration significantly induced eNOS activation and PDE5A inhibition. ICT with lower dose had better effects than ICA. In summary, ICT is more effective in preventing MCT-induced PAH in rats via NO/cGMP activation compared with ICA. These findings demonstrate a novel mechanism of the action of ICT that may have value in prevention of PAH., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Adverse conditions during early developmental stages permanently modify the metabolic function of organisms through epigenetic changes. Exposure to high sugar diets during gestation and/or lactation affects susceptibility to metabolic syndrome or hypertension in adulthood. The effect of a high sugar diet for shorter time lapses remains unclear. Here we studied the effect of short-term sucrose ingestion near weaning (postnatal days 12 and 28) (STS) and its effect after long-term ingestion, for a period of seven months (LTS) in rats. Rats receiving sucrose for seven months develop metabolic syndrome (MS). The mechanisms underlying hypertension in this model and those that underlie the effects of short-term exposure have not been studied. We explore NO and endothelin-1 concentration, endothelial nitric oxide synthase (eNOS) expression, fatty acid participation and the involvement of oxidative stress (OS) after LTS and STS. Blood pressure increased to similar levels in adult rats that received sucrose during short- and long-term glucose exposure. The endothelin-1 concentration increased only in LTS rats. eNOS and SOD2 expression determined by Western blot and total antioxidant capacity were diminished in both groups. Saturated fatty acids and arachidonic acid were only decreased in LTS rats. In conclusion, a high-sugar diet during STS increases the hypertension predisposition in adulthood to as high a level as LTS, and the mechanisms involved have similarities (participation of OS and eNOS and SOD expression) and differences (fatty acids and arachidonic acid only participate in LTS and an elevated level of endothelin-1 was only found in LTS) in both conditions. Changes in the diet during short exposure times in early developmental stages have long-lasting effects in determining hypertension susceptibility.

Objectives: To evaluate the performance of a combination of angiogenic and vasoactive biomarkers to predict the development of severe pre-eclampsia (PE)/HELLP syndrome in the third trimester., Methods: Included were 215 women referred in the third trimester to an obstetric outpatient clinic with suspected PE (mean gestational age, 35 + 4 weeks), and 94 with normal pregnancy attending a midwife clinic. Cases were categorized as having subclinical PE, essential hypertension, gestational hypertension, moderate PE, and severe PE/HELLP syndrome. Blood samples were analyzed by immunoassay and groups were compared with respect to potential clinical and biochemical biomarkers, with the primary outcome being development of severe PE/HELLP syndrome within 1 week and within 2 weeks of analysis. The most promising markers were also assessed in combination., Results: In the patients presenting with mild to moderate symptoms of PE, the individual markers which performed best for the prediction of progression to severe PE/HELLP syndrome within 1 week and within 2 weeks of biomarker evaluation were C-terminal pro-endothelin-1 (CT-pro-ET-1) (area under the receiver-operating characteristics curve (AUC), 0.82 and 0.78, respectively), soluble fms-like tyrosine kinase-1 (sFlt-1) (AUC, 0.81 and 0.76), systolic blood pressure (AUC, 0.80 and 0.68) and midregional pro-atrial natriuretic peptide (AUC, 0.79 and 0.77). The combination of biomarkers with the best performance was CT-pro-ET-1, sFlt-1 and systolic blood pressure, achieving an AUC of 0.94 for prediction of development of severe PE/HELLP syndrome within 1 week and an AUC of 0.83 for prediction of their development within 2 weeks of biomarker evaluation., Conclusions: The performance of CT-pro-ET-1 for prediction of the development of PE/HELLP syndrome in the third trimester was promising, especially in combination with sFlt-1 and systolic blood pressure. This was an exploratory study and our findings should be confirmed in further studies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

BACKGROUND No-reflow phenomenon is a well-known problem, often accompanying percutaneous coronary intervention (PCI) for ST-segment elevation acute myocardial infarction (STEAMI). This study investigated the value of plasma D-dimer and Endothelin-1 (ET-1) levels on admission in predicting no-reflow after primary PCI and long-term prognosis in STEAMI patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS There were 822 patients with STEAMI and T2DM undergoing successful primary PCI included in this study: 418 patients showed normal re-flow after PCI, while 404 patients showed no-reflow phenomenon after PCI. The predictive value of plasma ET-1 and D-dimer level, and other clinical parameters for the no-reflow phenomenon were analyzed. RESULTS The high plasma ET-1 and D-dimer levels showed predictive value for the no-reflow phenomenon in STEAMI patients with T2DM. Patients with high D-dimer and ET-1 levels showed higher risk (4.212, with 95%CI of 2.973-5.967 and 2.447 with 95%CI of 1.723-3.476, respectively) of no-reflow phenomenon compared with patients with low plasma D-dimer and ET-1 levels. Sensitivity of high plasma ET-1 and D-dimer levels in predicting no-reflow was 0.766. Both plasma D-dimer and ET-1 were adverse prognosticators for STEAMI patients with a T2DM post PCI (P<0.001). CONCLUSIONS In conclusion, plasma D-dimer and ET-1 levels on admission independently predict no-reflow after PCI in STEAMI patients with T2DM. When combined, the D-dimer and ET-1 levels as predictive and prognostic values are clinically promising. The plasma D-dimer and ET-1 levels provided a novel marker for treatment selection for the STEAIM patients with a T2DM history.

The aim of this study was to evaluate the effect of virgin olive oils (VOOs) enriched with phenolic compounds and triterpenes on metabolic syndrome and endothelial function biomarkers in healthy adults. The trial was a three-week randomized, crossover, controlled, double-blind, intervention study involving 58 subjects supplemented with a daily dose (30 mL) of three oils: (1) a VOO (124 ppm of phenolic compounds and 86 ppm of triterpenes); (2) an optimized VOO (OVOO) (490 ppm of phenolic compounds and 86 ppm of triterpenes); and (3) a functional olive oil (FOO) high in phenolic compounds (487 ppm) and enriched with triterpenes (389 ppm). Metabolic syndrome and endothelial function biomarkers were determined in vivo and ex vivo. Plasma high density lipoprotein cholesterol (HDLc) increased after the OVOO intake. Plasma endothelin-1 levels decreased after the intake of the three olive oils, and in blood cell cultures challenged. Daily intake of VOO enriched in phenolic compounds improved plasma HDLc, although no differences were found at the end of the three interventions, while VOO with at least 124 ppm of phenolic compounds, regardless of the triterpenes content improved the systemic endothelin-1 levels in vivo and ex vivo. No effect of triterpenes was observed after three weeks of interventions. Results need to be confirmed in subjects with metabolic syndrome and impaired endothelial function (Clinical Trials number NCT02520739).

This study investigated effects of grape consumption on biomarkers of cardiovascular health in obese participants in both postprandial and chronic settings. Twenty obese adults participated in this randomized, placebo controlled, double-blinded crossover trial. Participants were randomized to consume 60 g freeze-dried polyphenol-rich whole grape powder (GP) or placebo (PBO) followed by high fat high carbohydrate (HFHC) meal challenge. Following acute challenge, participants consumed their respective treatment daily for 4 weeks to determine effects of chronic consumption. Consumption of GP with HFHC meal significantly increased nuclear factor (erythroid-derived 2)-like 2 (NRF2) expression in peripheral blood mononuclear cells (PBMC) at 3 h (p < 0.05) and decreased plasma endothelin-1 (ET-1) concentration at 5 h (p < 0.05) after meal challenge compared with PBO. Following 4 weeks of daily GP consumption, soluble vascular cell adhesion molecule 1 (sVCAM-1) plasma concentration increased compared with PBO (p < 0.05), however baseline values differed between treatments. In conclusion, GP consumption resulted in decreased vasoconstrictor ET-1 concentration and increased gene expression related to oxidative stress defense following HFHC meal. Except for increase in sVCAM-1 concentration, 4 weeks of chronic GP consumption had little effect on cardiovascular biomarkers measured in this study. This trial was registered: clinicaltrials.gov NCT01674231., (Copyright © 2018. Published by Elsevier Inc.)

Endothelin-1 (ET-1) is associated with endothelial dysfunction and vasoconstriction. Increased circulating ET-1 levels are associated with long-term cardiovascular mortality. Renalase, released from kidney, metabolizes catecholamines and regulates blood pressure. An increase in circulating renalase levels has been reported in patients with chronic kidney disease (CKD) and is associated with coronary artery disease (CAD). We hypothesized the existence of a synergistic effect of serum renalase levels and CKD on ET-1 levels in patients with CAD. We evaluated 342 non-diabetic patients with established CAD. ET-1 and renalase levels were measured in all patients after an overnight fast. Patients with CKD had higher ET-1 (1.95 ± 0.77 vs. 1.62 ± 0.76 pg/ml, P < 0.001) and renalase levels (46.8 ± 17.1 vs. 33.9 ± 9.9 ng/ml, P < 0.001) than patients without CKD. Patients with both CKD and high renalase levels (>the median of 36.2 ng/ml) exhibited the highest serum ET-1 (P value for the trend <0.001). According to multivariate linear regression analysis, the combination of high serum renalase levels with CKD was a significant risk factor for increased serum ET-1 levels (regression coefficient = 0.297, 95% confidence interval = 0.063‒0.531, P = 0.013). In conclusion, our data suggest a synergistic effect of high serum renalase levels and CKD on increases in ET-1 levels in patients with established CAD.

Background and Aims: The prognostic role of big endothelin-1 (ET-1) in atrial fibrillation (AF) is unclear. We aimed to assess its predictive value in patients with AF., Methods: A total of 716 AF patients were enrolled and divided into two groups based on the optimal cut-off value of big ET-1 in predicting all-cause mortality. The primary outcomes were all-cause mortality and major adverse events (MAEs). Cox regression analysis and net reclassification improvement (NRI) analysis were performed to assess the predictive value of big ET-1 on outcomes., Results: With the optimal cut-off value of 0.55 pmol/L, 326 patients were classified into the high big ET-1 levels group. Cardiac dysfunction and left atrial dilation were factors related to high big ET-1 levels. During a median follow-up of 3 years, patients with big ET-1 ≥ 0.55 pmol/L had notably higher risk of all-cause death (44.8% vs. 11.5%, p < 0.001), MAEs (51.8% vs. 17.4%, p < 0.001), cardiovascular death, major bleeding, and tended to have higher thromboembolic risk. After adjusting for confounding factors, high big ET-1 level was an independent predictor of all-cause mortality (hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.46-3.05; p < 0.001), MAEs (HR 2.05, 95% CI 1.50-2.80; p = 0.001), and cardiovascular death (HR 2.44, 95% CI 1.52-3.93; p < 0.001). NRI analysis showed that big ET-1 allowed a significant improvement of 0.32 in the accuracy of predicting the risk of both all-cause mortality and MAEs., Conclusions: Elevated big ET-1 levels is an independent predictor of long-term all-cause mortality, MAEs, and cardiovascular death in patients with AF., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Endothelial cells (ECs) constitute the defensive barrier of vasculature, which maintains the vascular homeostasis. Mitochondrial oxidative stress (mitoOS) in ECs significantly affects the initiation and progression of vascular diseases. The higher serum thyroid stimulating hormone (TSH) level is being recognized as a nonconventional risk factor responsible for the increased risk of cardiovascular diseases in subclinical hypothyroidism (SCH). However, effects and underlying mechanisms of elevated TSH on ECs are still ambiguous. We sought to investigate whether cyclophilin D (CypD), emerging as a crucial mediator in mitoOS, regulates effects of TSH on ECs., Methods and Results: SCH patients with TSH > = 10mIU/L showed a positive correlation between serum TSH and endothelin-1 levels. When TSH levels declined to normal in these subjects after levothyroxine therapy, serum endothelin-1 levels were significantly reduced. Supplemented with exogenous thyroxine to keep normal thyroid hormones, thyroid-specific TSH receptor (TSHR)-knockout mice with injection of exogenous TSH exhibited elevated serum TSH levels, significant endothelial oxidative injuries and disturbed endothelium-dependent vasodilation. However, Tshr -/- mice resisted to TSH-impaired vasotonia. We further confirmed that elevated TSH triggered excessive mitochondrial permeability transition pore (mPTP) opening and mitochondrial oxidative damages in mouse aorta, as well as in cultured ECs. Genetic or pharmacological inhibition of CypD (the key regulator for mPTP opening) attenuated TSH-induced mitochondrial oxidative damages and further rescued endothelial functions. Finally, we confirmed that elevated TSH could activate CypD by enhancing CypD acetylation via inhibiting adenosine monophosphate-activated protein kinase/sirtuin-3 signaling pathway in ECs., Conclusions: These findings reveal that elevated TSH triggers mitochondrial perturbations in ECs and provide insights that blocking mitochondrial CypD enhances the defensive ability of ECs under TSH exposure., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To study the endothelial dysfunction by measuring Nitric Oxide and Endothelin-1, and inter-genotypic variation of inducible Nitric Oxide Synthase gene (C150T) polymorphism among the study subjects., Methods: 50 diagnosed cases of metabolic syndrome as per International Diabetes Federation (IDF) criteria and 50 healthy volunteers as control were enrolled. Nitric Oxide, Endothelin were measured and PCR-RFLP was done to identify the iNOS gene C150T polymorphism and its effect on serum nitric oxide levels., Results: Subjects with metabolic syndrome had lower NO levels (16.3 ± 10.3 vs 20.9 ± 11 µM, p = 0.032) and higher endothelin (2.68 ± 1.73 vs 1.98 ± 0.82 fmol/ml, p = 0.011). The frequency of mutant T allele (10% vs 9%) was higher in cases. Serum nitric oxide levels were lower in cases expressing the Mutant T allele as compared to wild type C allele. However, the differences were not statistically significant., Conclusions: The present study demonstrated that iNOS C150T polymorphism did not show significant association with metabolic syndrome. Serum nitric oxide levels could be influenced by factors other than genetic polymorphism of iNOS gene (C150T) which cause endothelial dysfunction in metabolic syndrome and associated co-morbidities.

Endothelial dysfunction is one of the main pathological changes in Obstructive sleep apnoea (OSA). The Rho kinase (ROCK) pathway is associated with endothelial dysfunction. However, the interaction between ROCK and nuclear factor of activated T cells isoform c3 (NFATc3) in the development of this pathological response under chronic intermittent hypoxia (CIH) is unclear. To simulate the OSA model, we established a moderate CIH rat model by administering the fraction of inspired O2 (FiO2) from 21% to 9%, 20 times/h, 8 h/day for 3 weeks. Fasudil (ROCK inhibitor, 8 mg/kg/d, i.p.) was administrated in the rats exposed to CIH for 3 weeks. Our results demonstrated that CIH caused significantly endothelial dysfunction, accompanying with increased ET-1 level, decreased eNOS expression and NO production, which reduced ACh-induced vascular relaxation responses. Moreover, RhoA/ROCK-2/NFATc3 expressions were up-regulated. Fasudil significantly improved CIH induced endothelial dysfunction. Data suggested that the ROCK activation is necessary for endothelial dysfunction during CIH.

Objective: To evaluate the efficacy and safety of Tongxinluo Capsule (, TXL) for patients with cardiac syndrome X (CSX)., Methods: Randomized controlled trials (RCTs) regarding TXL in the treatment of CSX were searched in Chinese Biomedicine Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, PubMed, EMBASE, Cochrane Central Register of Controlled Trial, websites of the Chinese and International Clinical Trial Registry platform up to June 30, 2015. The intervention was either TXL alone or TXL combined with conventional treatment, while the control intervention was conventional treatment with or without placebo. Data extraction, methodological quality assessment and data analyses were performed according to the Cochrane criteria. The primary outcome was a composite event of death, acute myocardial infarction (AMI), angina requiring hospitalization, revascularization, and heart failure. The secondary outcome measures were angina symptom improvement, electrocardiograph (ECG) improvement, and serum endothelin-1 (ET-1) level. The adverse events were also recorded. RevMan 5.3 software was applied for data analyses., Results: Twelve RCTs (696 patients) were included. Compared with conventional treatment, the addition of TXL to conventional treatment showed some benefits on relieving angina symptoms [risk ratio (RR): 1.46, 95% confidence interval (CI) (1.25, 1.71), P<0.01], and improving ECG [RR: 1.45, 95% CI (1.21, 1.74), P<0.01]. The pooled result did not support a benefit of TXL on reducing the incidence of primary outcome [RR: 0.20, 95% CI (0.02, 1.61), P=0.13]. In addition, TXL decreased serum ET-1 concentration of CSX patients [standardized mean number:-1.63, 95% CI (-2.29,-0.96), P<0.01]. No serious adverse events were reported., Conclusions: TXL documents potential benefits on attenuating angina symptoms, improving ECG and decreasing serum ET-1 level for CSX patients. However, more rigorous RCTs with high quality are needed to confirm its efficacy and safety.

Aim: To evaluate the role of adenovirus-mediated transduction human VEGF isoform 165 via direct myocardial injection in rats with an occluded circumflex coronary artery, and the possible underlying mechanism., Methods: Sprague-Dawley rats were induced myocardial infarction (MI) with ligation of the left coronary artery. Rats were randomly divided into 4 groups: 1) the sham group; 2) the MI group; 3) the NS (normal saline) group and 4) the VEGF group. Direct myocardial injection of 0.1 ml rAAV-hVEGF165 (virus titer, 2×10 10 v.p./ml) was performed in the border zone of myocardial infarction in the VEGF group at 3 different sites, whereas 0.1 ml of normal saline was injected in the NS group. 4 weeks after treatment, the serum levels of atrial natriuretic peptide (ANP), angiotensin-II (Ang II), tumor necrosis factor-α (TNF-α), and endothelin-1 (ET-1) were detected by competitive radioimmunoassay. The level of VEGF, Bax, and Bcl-2 was assessed by IHC., Results: The whole heart weight, left heart weight, heart mass index and left heart mass index in the VEGF group were higher than those in the MI and NS group. VEGF treatment could also significantly increase cardiac function, and increase microvessel density in the infarcted area. Moreover, VEGF treatment could decrease the serum neurohumoral factors (ANP, Ag II, and TE-1), and inhibit myocardial apoptosis via TNF-α, Bax, and Bcl-2., Conclusion: Adenovirus-mediated VEGF165 gene therapy could significantly improve cardiac function possibly by inducing myocardial collateral vessel development, inhibiting the apoptosis of myocardial cells, and inhibiting ventricular remodeling., (© 2018 by the Association of Clinical Scientists, Inc.)

Purpose: To evaluate the circulatory levels of endothelin 1 (ET-1) and the placental alkaline phosphatase (ALP) in pregnant women with placenta percreta (PP) and a control group., Methods: This study was carried out in the Obstetrics and Gynecology and in the Biochemistry Departments of Harran University Medical School. Forty-four women who underwent cesarean section (CS) due to PP and 44 women who underwent CS for other obstetric reasons were included in this study. The PP diagnosis was made by a pathologic examination that showed an extreme trophoblastic invasion involving the uterine serosa.The levels of circulating ET-1 and placental ALP were measured by an enzyme-linked immunosorbent assay (ELISA)., Results: Women with PP more frequently received antenatal steroids and blood transfusions and they delivered at an earlier gestational age compared to controls. In women with PP, preoperative circulating ET-1 and placental ALP levels were lower than in the controls (p < .05 for both)., Conclusions: The findings suggest that a decrease in ET-1 and placental ALP levels might play a role in the pathogenesis of PP.

Introduction: Exposure to air pollution impairs aspects of endothelial function such as flow-mediated dilation (FMD). Outdoor exercisers are frequently exposed to air pollution, but how exercising in air pollution affects endothelial function and how these effects are modified by exercise intensity are poorly understood., Objectives: Therefore, the purpose of this study was to determine the effects of low-intensity and high-intensity cycling with diesel exhaust (DE) exposure on FMD, blood pressure, plasma nitrite and nitrate (NOx) and endothelin-1., Methods: Eighteen males performed 30-minute trials of low or high-intensity cycling (30% and 60% of power at VO2peak) or a resting control condition. For each subject, each trial was performed once while breathing filtered air (FA) and once while breathing DE (300ug/m3 of PM2.5, six trials in total). Preceding exposure, immediately post-exposure, 1 hour and 2 hours post-exposure, FMD, blood pressure and plasma endothelin-1 and NOx concentrations were measured. Data were analyzed using repeated-measures ANOVA and linear mixed model., Results: Following exercise in DE, plasma NOx significantly increased and was significantly greater than FA (p<0.05). Two hours following DE exposure, endothelin-1 was significantly less than FA (p = 0.037) but exercise intensity did not modify this response. DE exposure did not affect FMD or blood pressure., Conclusion: Our results suggest that exercising in DE did not adversely affect plasma NOX, endothelin-1, FMD and blood pressure. Therefore, recommendations for healthy individuals to moderate or avoid exercise during bouts of high pollution appear to have no acute protective effect.

Background: Breathlessness is the most common symptom in people with pulmonary arterial hypertension and congenital heart disease (CHD-APAH), previously thought to be caused by worsening PAH, but perhaps also by inflammation and abnormalities of lung function. We studied lung function and airway inflammation in patients with CHD-APAH and compared the results with controls., Methods and Results: Sixty people were recruited into the study: 20 CHD-APAH, 20 CHD controls, and 20 healthy controls. Spirometry, gas transfer, whole body plethysmography and lung clearance index, 6-minute walk distance, and medical research council dyspnea scoring were performed. Inflammatory markers and endothelin-1 levels were determined in blood and induced sputum. The CHD-APAH group had abnormal lung function with lung restriction, airway obstruction, and ventilation heterogeneity. Inverse correlations were shown for CHD-APAH between medical research council dyspnea score and percent predicted peak expiratory flow ( r =-0.5383, P =0.0174), percent predicted forced expiratory flow rate at 50% of forced vital capacity ( r =-0.5316, P =0.0192), as well as for percent predicted forced expiratory volume in 1 s ( r =-0.6662, P =0.0018) and percent predicted forced vital capacity ( r =-0.5536, P =0.0186). The CHD-APAH patients were more breathless with lower 6-minute walk distance (360 m versus 558 m versus 622 m, P =0.00001). Endothelin-1, interleukin (IL)-β, IL-6, IL-8, tumor necrosis factor α, and vascular endothelial growth factor were significantly higher in CHD-APAH than controls. Serum endothelin-1 for CHD-APAH correlated with airflow obstruction with significant negative correlations with percent predicted forced expiratory flow rate at 75% of forced vital capacity ( r =-0.5858, P =0.0135)., Conclusions: Raised biomarkers for inflammation were found in CHD-APAH. Significant abnormalities in airway physiology may contribute to the dyspnea but are not driven by inflammation as assessed by circulating and sputum cytokines. A relationship between increased serum endothelin-1 and airway dysfunction may relate to its bronchoconstrictive properties., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

To investigate the therapeutic mechanisms underlying prostaglandin E1 (PGE1) and angiotensin-converting enzyme inhibitor (ACEI) on reducing urinary protein in diabetic kidney disease (DKD). DKD rats were established and randomly divided into four groups: PGE1 (10 μg/kg/day) (P group), ACEI (10 mg/kg/day) (A group), combination of PGE1 with ACEI treatment (P + A group), and saline treatment group (DKD group). Untreated rats were used as normal control (N group). Urinary albumin, endothelin-1 (ET-1), angiotensin II (AngII), TUNEL assay, Masson's trichrome staining, and immunohistochemistry staining for CD68 were evaluated in all groups. Ten days after treatment, urinary albumin was significantly decreased in the P and P + A groups (p < 0.01 vs. the DKD group). At the end of 8 weeks, the albumin was still significantly reduced in the P + A group (p < 0.05 vs. the A group). ET-1 and AngII were also significantly decreased in three treatment groups (p < 0.01 vs. the DKD group), especially in the P + A group. Few cells underwent apoptosis in glomerular regions in DKD rats, while amounts of apoptotic cells were seen in tubules regions. Further, apoptosis and the areas of fibrosis in tubulointerstitial were both decreased most in the P + A group compared with the DKD group. Apoptosis of renal tubular epithelial cells may participate in the development and progression of DKD in rats. Combination of PGE1 with AGEI remarkably protects renal function compared with PGE1 or ACEI monotherapy. The potential therapeutic mechanisms of PGE1 and AGEI might be via multiple targets and, at least in part, through inhibiting the apoptosis of renal tubular epithelial cells.

Aim - to study the state of the microcirculatory bed and the endothelial system in patients at risk of developing reperfusion syndrome and suggest methods for their correction. The work included 29 patients with obliterating diseases of the abdominal aorta and lower limb arteries with a high risk of developing reperfusion complications. Two groups of patients were identified. Group I - 8 patients, preoperative preparation include the generally accepted approaches. Group II - 21 patients whose preoperative preparation included, in addition to preparations for improving rheological blood conditions, prolonged epidural anesthesia, intravenous injection of hydroxyethylstarches, korvetin and alprostadil. In patients of both groups, a study was made of the state of the level of endothelial dysfunction, changes in capillary blood flow and arterio-venular blood shunting. Revascularization of the lower limbs in patients with a high risk of developing reperfusion complications leads to a deepening of endothelial dysfunction. The latter is characterized by a 2.3-fold increase (p<0.001) in the early postoperative period of circulating endothelial cells in the blood, by 2.5 times (p <0.001) endothelin-1, while a 1.3-fold decrease (p<0,05) P-selectin and in 1,7 times (p<0,05) E-selectin. The depth of the lesion of the endothelial system is indicated by a decrease of 29.9 % (p<0.001) in the level of NO. Deepening of endothelial dysfunction after reconstructive-reconstructive surgery is reflected in violations of the function of the microcirculatory bed. It is characterized by a 1.9-fold decrease (p<0.001) of skin perfusion, 2.0 times (p<0.001) in the erythrocyte concentration index and a 14% decrease (p<0.05) in capillary blood flow. This is facilitated by an increase of 14% (p<0.05) in skin perfusion pressure and an increase of 16% (p<0.05) in the resistance index of the microcirculatory bed, which leads to a decrease in tissue oxygenation to a level 3.38±0.14 mm.hg.

Introduction: Hemodialysis (HD) patients have altered pulmonary function and this is associated with impaired endothelial function and cardiovascular events. Respiratory muscle training (RMT) has the potential to improve cardiovascular outcomes in patients undergoing maintenance HD. Here, we evaluated the effects of RMT on endothelium/glycocalyx, oxidative stress biomarkers and pulmonary function test in HD patients., Methods: This is a randomized controlled clinical trial including 41 patients undergoing thrice-weekly maintenance HD. Patients were randomly assigned at a 2:1 ratio to receive or not RMT during HD sessions for 8 weeks. Main outcomes were changes in levels of the biomarkers related to endothelium activation (vascular cell adhesion molecule 1, VCAM-1, and intercellular adhesion molecule 1, ICAM-1), glycocalyx derangement (syndecan-1), aberrant angiogenesis (angiopoietin-2) and oxidative stress (malondialdehyde) compared to baseline. Also, maximal inspiratory/expiratory pressure (MIP, MEP), Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) were evaluated. Other outcomes included changes in functional capacity and pulmonary function test. We also performed a post-hoc analysis of plasma endothelin-1 levels., Results: Of 56 randomly assigned patients, 41 were included in the primary final analyses. RMT increased all pulmonary function parameters evaluated and significantly reduced plasma syndecan-1 levels at 8 weeks compared to placebo (between-group difference: -84.5; 95% CI, -148.1 to -20.9). Also, there was a reduction in plasma levels of angiopoietin-2 (between-group difference: -0.48; 95% CI, -1.03 to -0.097). Moreover, there was a significant reduction in mean blood pressure at rest (between-group difference: -12.2; 95%CI, -17.8 to -6.6) associated with a reduction in endothelin-1 levels (between-group difference: -0.164; 95% CI, -0.293 to -0.034). There was no difference regarding biomarkers of endothelial activation or oxidative stress., Conclusion: A short-term RMT program ameliorate FVC, FEV1 and reduces syndecan-1 and angiopoietin-2 biomarker levels. Finally, better blood pressure control was attained during training and it was associated with a reduction in endothelin-1 levels., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the influence of dexmedetomidine on myocardial ischemia-reperfusion injury (IRI) in rabbits., Methods: Twenty-four New Zealand white rabbits were randomly divided into two equal-sized groups: IRI group (group IR) and dexmedetomidine group (group D). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular diastolic pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax were recorded and calculated at the following time points: before (T0) and after (T1) dexmedetomidine infusion, after 30-min ischemia (T2), and after 120-min reperfusion (T3). The levels of plasma endothelin 1 (ET-1), thromboxane A2 (TXA2), and platelet activating factor (PAF); area of myocardial infarction (MI); and no-reflow area were evaluated., Results: SBP, DBP, LVSP, LVEDP, LVDP, and +dp/dtmax at T3 were higher in group D than in group IR (P<0.05). The average no-reflow area in group IR was significantly smaller than that in group D (14±3% vs. 38±5%, P=0.0116). The ET-1, TXA2, and PAF levels at T2 and T3 were higher than those at T0 in both groups (P<0.05)., Conclusion: Dexmedetomidine could reduce the magnitude of ischemic myocardial no-reflow area and protect the myocardium with ischemia-reperfusion injury.

Objective: Introduction: the purpose of the research consisted in the study of the functional state of the endothelium in patients having persistent asthma (A) with an uncontrolled course in combination with diabetes mellitus type 2 (DM2T) and obesity (O) The aim: on the basis of a complex study of nitric oxide metabolites (nitrosothiols, S-NO), von Willebrand factor (VWF) and endothelin-1 (EТ-1)., Patients and Methods: Materials and methods: The study involved 90 A patients with comorbid states, who were divided into 3 groups. Group 1 included patients with A, group 2 consisted of A with DM2T (A+DM2T), group 3 was composed of A and obesity (A+O); the control group had 21 persons., Results: Results: Lower S-NO levels in patients from groups 2 and 3 and an increase of ET-1 in these groups versus the control one demonstrate an imbalance of the indices, which produce an effect on the vascular tone. Statistically, the activity of VWF as the marker of an endothelial damage was significantly higher: it was 169.0 (147.0;178.50) in cases from group 2 and 156.0 (142.75;165.0) in those from the group of A+O. Thus, indices of a disrupted endothelial function were more expressed in patients from group 2. Positive relations of ET-1 with VWF and negative ones with S-NO., Conclusion: Conclusions: The conducted study has proved that the endothelial function in patients with A+DM2T and A+O is characterized by a disturbed relationship between relaxing and constricting endothelial factors. The obtained data make it possible to receive an opportunity to correct the above impairments in future.

Objectives: This study analysed the association between endothelin-1 (ET-1) and left atrial dimension (LAD) and evaluated whether ET-1 can be a predictor of postoperative atrial fibrillation (POAF) after mitral valve surgery., Methods: This is a prospective study that enrolled 80 patients who underwent isolated mitral valve surgery. Plasma concentrations of ET-1 from peripheral venous blood were tested. POAF was detected using a telemetry strip or 12-lead electrocardiogram until the time of discharge., Results: Patients undergoing mitral valve surgery with preoperative sinus rhythm (n = 80; average age 63.9 ± 7.9 years) were recruited to this study. POAF was documented in 31 (38.8%) patients. Preoperative plasma ET-1 levels were higher in patients with POAF compared to those without POAF (2.23 ± 0.67 vs 1.68 ± 0.59 pg/ml; P < 0.001). The plasma concentrations of ET-1 were positively correlated with LAD (Pearson's r = 0.421; P < 0.001). Multivariate logistic regression analysis revealed that LAD (odds ratio 1.170, 95% confidence interval 1.039-1.317; P = 0.009) and preoperative plasma ET-1 levels (upper versus lower 50th percentile: odds ratio 3.713, 95% confidence interval 1.085-12.701; P = 0.037) were predictors of POAF after mitral valve surgery., Conclusions: Plasma levels of ET-1 were positively correlated with LAD in patients with mitral valve disease. An elevated preoperative plasma ET-1 level can be used as a predictor of POAF after mitral valve surgery., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, or non-hereditary, chronic demyelinating neuropathy. Currently, there is no reliable molecular biomarker that can identify CIDP patients as well as monitor disease severity., Material and Methods: We measured serum levels of endothelin-1 (ET-1), a factors involved in vasoconstrictive, inflammatory and nerve regenerative processes, in 20 CIDP, 21 acute inflammatory demyelinating polyneuropathy (AIDP), 37 multiple sclerosis (MS), and 10 Alzheimer's disease (AD) patients, as well as 26 healthy control (HC) subjects., Results: Patients with CIDP demonstrated higher serum levels of ET-1 (2.07±1.07pg/mL) than those with AIDP (0.75±0.62ng/mL, P<0.001), AD (0.78±0.49pg/mL, P<0.001), as well as HCs (1.16±0.63pg/mL, P=0.002), while levels of ET-1 in patients with MS (2.10±0.81pg/mL) and CIDP were similar. Furthermore, the serum ET-1 levels significantly correlated with Inflammatory Neuropathy Cause And Treatment (INCAT) disability scale in CIDP patients. Receiver operating characteristic (ROC) curve showed good discrimination ability for ET-1 to distinguish CIDP patients from AIDP (AUC=0.883) or HCs (AUC=0.763)., Conclusion: This study discloses the potential of serum ET-1 as a biomarker for CIDP., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Mechanical ventilation (MV) is routinely used in pediatric general anesthesia and critical care, but may adversely affect the cardiocirculatory system. Biomarkers are increasingly measured to assess cardiovascular status and improve clinical treatment decision-making. As the impact of mechanical ventilation strategies on cardiovascular biomarkers in ventilated infants is largely unknown, we conducted this retrospective study in a healthy in vivo infant rat ventilation model using 14-days old Wistar rats. We hypothesized that 2 h of mechanical ventilation with high and low positive end-expiratory pressure (PEEP), hyperoxemia, hypoxemia, hypercapnia, and hypocapnia would significantly impact B-type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), and endothelin-1 (ET-1). We found BNP to be driven by both high (9 cmH 2 O) and low (1 cmH 2 O) PEEP compared to ventilated control animals (P < 0.05). VEGF concentrations were associated with high PEEP, hyperoxemia, hypoxemia, and hypocapnia (P < 0.05), whereas ET-1 levels were changed only in response to hypoxemia (P < 0.05). In conclusion, the mode of mechanical ventilation alters plasma biomarker concentrations. Moreover, BNP and VEGF might serve as surrogate parameters for ventilation induced cardiovascular compromise and lung tissue damage. Furthermore, our data support the hypothesis, that sudden onset of hyperoxemia may trigger a quick VEGF release as a possible cellular survival reflex., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

The association of poor outcome and mortality with low levels of hemoglobin (Hb) and hematocrit (HcT) in patients admitted after acute Ischemic Stroke (IS) was recently demonstrated. The mechanisms behind this still remain unclear. Our study aims to find out whether mRNA expressions and plasma concentrations of endothelin-1 (ET-l), endothelin-2 (ET-2) and endothelin-3 (ET-3) remain different in IS sufferers with low HcT and Hb levels in comparison with those whose HcT i Hb levels during a severe IS episode remain within the norm. The study included 60 patients treated consecutively for first-time IS. The assessment of mRNA gene expression and plasma concentration of ET-1, ET-2, ET-3 was conducted in the first, third and seventh day following the onset of stroke using qRT-PCR method and ELISA tests. We demonstrated that patients whose initial HcT and Hb levels were below the norm presented a deeper neurologic deficit on 1, 3 and 7 day following stroke with noticeable improvement no earlier than between day 3 and 7. We also found a negative correlation between the initial HcT and Hb and concentration of plasma ET-1 on the same days. The patients whose HcT and Hb levels were within normal limits showed a significant improvement in their neurologic condition on each consecutive day of the observation. Reduced levels of Hb and HcT combined with an increased plasma concentration of vasoconstrictive endothelin-1 are strongly associated with poor outcome and high mortality in acute ischemic stroke., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

This study aimed to investigate the antihypertensive effect and possible mechanism of Dendrobium officinale flos on hypertensive rats induced by high glucose and high fat compound alcohol. The hypertensive models were successfully made by high-glucose and high-fat diet, with gradient drinking for 4 weeks, and then divided into model control group, valsartan (5.7 mg·kg⁻¹) positive control group and D. officinale flos groups (3，1 g·kg⁻¹). After 6 weeks of treatment, the blood pressure of rats was measured regularly. After the last administration, endothelin-1 (ET-1), thromboxane B₂ (TXB₂), prostacyclin (PGI₂) and nitric oxide (NO) were tested. Endothelial nitric oxide synthase (eNOS) expression and lesion status in thoracic aorta were detected. The vascular endothelium dependent dilation of the thoracic aorta was detected by the isolated vascular loop tension test. The results showed that D. officinale flos could significantly reduce systolic blood pressure and mean arterial pressure in hypertensive rats, inhibit the thickening of thoracic aorta and the loss of endothelial cells, reduce plasma content of ET-1 and TXB₂, and increase the content of PGI₂ and NO. After long-term administration, vascular endothelium dependent dilation of the thoracic aorta was significantly increased, and could be blocked by the eNOS inhibitor (L-NAME) and increase the expression of eNOS. Therefore, D. officinale flos has an obvious antihypertensive effect on high glucose and high fat compound alcohol-induced hypertensive rats. Its mechanism may be correlated with the improvement of vascular diastolic function by protecting vascular endothelial cells, and finally resist hypertension., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Psoriatic lesions are characterized by hyperproliferation, aberrant differentiation of keratinocytes resistant to apoptosis and inflammation. miR-31 plays pro-proliferative, pro-differentiative and pro-inflammatory roles and modulates apoptosis in psoriatic keratinocytes. Endothelin-1 (ET-1) is produced by psoriatic keratinocytes and suppresses apoptosis. Inflammation increases the production of ET-1, which in turn leads to the chronic stimulation of keratinocyte proliferation. The aim of this study was to identify the putative link between two potential biomarkers (miR-31 and ET-1) in patients with psoriasis. The study design included experimental group (29 patients with psoriasis), and the control group (22 blood donors). The PASI score evaluated the state of the disease (median: 18.6; interquartile range 14.5-20.9). Both, the serum level of ET-1 and the whole blood level of miR-31 were significantly increased (p<0.001 and p<0.05, respectively) in patients compared to the controls. However, a significant negative relationship between ET-1 and miR-31 was observed (Spearman's rho=-037, p=0.05). It is possible that a negative feedback loop will be present between miR-31 and ET-1. Our results indicate that miR-31 and ET-1, potential biomarkers of the disease, play significant roles in the pathophysiology of psoriasis.

Background: The early detection of cardiac syncope is challenging. We aimed to evaluate the diagnostic value of 4 novel prohormones, quantifying different neurohumoral pathways, possibly involved in the pathophysiological features of cardiac syncope: midregional-pro-A-type natriuretic peptide (MRproANP), C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin., Methods and Results: We prospectively enrolled unselected patients presenting with syncope to the emergency department (ED) in a diagnostic multicenter study. ED probability of cardiac syncope was quantified by the treating ED physician using a visual analogue scale. Prohormones were measured in a blinded manner. Two independent cardiologists adjudicated the final diagnosis on the basis of all clinical information, including 1-year follow-up. Among 689 patients, cardiac syncope was the adjudicated final diagnosis in 125 (18%). Plasma concentrations of MRproANP, C-terminal proendothelin 1, copeptin, and midregional-proadrenomedullin were all significantly higher in patients with cardiac syncope compared with patients with other causes ( P <0.001). The diagnostic accuracies for cardiac syncope, as quantified by the area under the curve, were 0.80 (95% confidence interval [CI], 0.76-0.84), 0.69 (95% CI, 0.64-0.74), 0.58 (95% CI, 0.52-0.63), and 0.68 (95% CI, 0.63-0.73), respectively. In conjunction with the ED probability (0.86; 95% CI, 0.82-0.90), MRproANP, but not the other prohormone, improved the area under the curve to 0.90 (95% CI, 0.87-0.93), which was significantly higher than for the ED probability alone ( P =0.003). An algorithm to rule out cardiac syncope combining an MRproANP level of <77 pmol/L and an ED probability of <20% had a sensitivity and a negative predictive value of 99%., Conclusions: The use of MRproANP significantly improves the early detection of cardiac syncope among unselected patients presenting to the ED with syncope., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01548352., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Most studies reported that high plasma endothelin-1 (ET-1), big ET-1, and C-terminal proET-1 (CT-proET-1) were correlated with poor prognosis of heart failure (HF). However, available evidence remains controversial. To help solve the debate, we collected all the available studies and performed a meta-analysis., Methods: We searched the databases covering Embase, PubMed, Ovid, and Web of Science on June 28, 2017. The hazard ratio (HR) or risk ratio (RR) and its 95% confidence intervals (CIs) were collected and calculated by use of a random-effect model. Heterogeneity was assessed by Cochran's Q test, and publication bias was assessed by funnel plots with Egger's and Begg's linear regression test., Results: Thirty-two studies with 18,497 patients were included in the analysis. Results showed that circulating ET-1, big ET-1, and CT-proET-1 were positively correlated with high risk of adverse outcomes, with pooled RRs (95% CIs) of 2.22 (1.82-2.71, P < .001), 2.47 (1.93-3.17, P < .001), and 2.27 (1.57-3.29, P < .001), respectively. In the subgroup of death as primary outcome, the pooled RRs (95% CIs) were 2.13 (1.68-2.70, P < .001), 2.55 (1.82-3.57, P < .001), and 2.02 (1.39-2.92, P < .001) for ET-1, big ET-1, and CT-proET-1, respectively. No significant publication bias was observed in this study., Conclusion: Our meta-analysis provided evidence that increased plasma levels of ET-1, big ET-1, and CT-proET-1 were associated with poor prognosis or mortality for HF populations., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Endothelial dysfunction has been considered as one of the important factors in pathogenesis of Metabolic Syndrome (Met S). Subclinical hypothyroidism (SCH) has also been reported to be associated with Met S. The aim of our study is to evaluate the association of raised TSH with mediators of endothelial dysfunction in Met S with Subclinical hypothyroidism as compared to healthy controls., Methods: Study population consisted of 100 subjects, out of which 50 were cases of Met S and 50 were healthy controls. Met S group were further divided into two, based on the presence & absence of SCH. Serum insulin, T3, T4, TSH were measured by chemiluminescence based immunoassay (CLIA). Serum nitric oxide (NO) levels were measured by Modified Griess's method and serum endothelin-1 (ET-1) levels were measured by ELISA., Results: Out of 50 cases of Met S, SCH was diagnosed in 22. The mean serum TSH levels were significantly higher in Met S cases as compared to healthy controls (5.7 ± 1.2 μIU/mL vs. 2.3 ± 1.6 μIU/mL, P <0.0001). Mean serum NO levels were significantly lower in Met S cases as compared to healthy control (15.4 ± 10 μM vs. 21 ± 10 μM, p = 0.009). Mean serum ET-1 levels were significantly higher in Met S cases as compared to healthy controls (2.68 ± 1.7 fmol/mL vs. 2.1 ± 0.84 fmol/mL, p = 0.011). On Pearson's correlation analysis, TSH showed positive correlation with ET-1 (r = 0.341, p = 0.001) and negative correlation with NO (r = -0.331, p = 0.001). Binary logistic regression analysis showed that TSH, NO and ET-1 has significant odd's ratio for predicting Met S., Conclusion: Met S cases were screened for thyroid abnormalities and found to have 44% of SCH along with co-existing endothelial dysfunction. Raised TSH in SCH could cause endothelial dysfunction which may lead to Met S and associated co-morbidities. Present study gives new insight in linking endothelial dysfunction and raised TSH in Met S. Therefore, Met S cases should be screened for SCH and treated appropriately to attenuate endothelial dysfunction and associated comorbidities in Met S.

The pathogenesis of the Crimean-Congo hemorrhagic fever (CCHF) and the cause of the hemorrhage are not yet fully understood. However, the endothelium plays a key role in the pathogenesis. The purpose of this study was to investigate endothelial dysfunction markers (asymmetrical dimethyl arginine [ADMA], endothelin 1[ET-1], thrombomodulin [TM], von Willebrand factor [vWf], and intercellular adhesion molecule [ICAM-1]) in serum in patients with CCHF and their associations with hemorrhage. Seventy-three patients with CCHF were included in the study. All patients' endothelial dysfunction markers were studied using routine biochemical and hematological tests. The data obtained were then subjected to statistical analysis. Statistically significant differences were determined between the patients and healthy control groups at time of presentation to hospital in terms of ADMA (P < 0.001), ET-1 (P < 0.001), TM (P = 0.039), vWf (P < 0.001), and ICAM-1 (P < 0.001) levels. Only the differences in TM and vWf were significant between the hemorrhagic and non-hemorrhagic groups (P < 0.05). Both serum ADMA and TM levels were significantly higher in the hemorrhage and non-hemorrhage CCHF groups on the 5th day compared to the 1st day (P < 0.05). Levels of endothelial dysfunction markers in CCHF vary in proportion to the damage occurring in the endothelium. ADMA and TM levels were lower in periods with mild endothelial injury. They were increased in line with severity endothelial injury. They may be an early marker in showing hemorrhage. Elevation in ADMA levels and low nitric oxide levels lead to endothelial injury and hemorrhage. Soluble TM that entered the circulation in line with the increased endothelial injury in hemorrhagic patients has been compromised the coagulation cascade., (© 2017 Wiley Periodicals, Inc.)

Introduction: Acute aerobic exercise prevents sitting-induced impairment of flow-mediated dilation (FMD). Further, evidence suggests that sitting-induced impairment of FMD occurs via an oxidative stress-dependent mechanism that disrupts endothelial function., Purpose: We hypothesized that acute aerobic exercise would prevent impairment of femoral artery FMD by limiting oxidative stress responses that increase endothelin-1 (ET-1) levels and disrupt nitric oxide (NO) status., Methods: In a randomized, cross-over study, healthy men (n = 11; 21.2 ± 1.9 years) completed two 3 h sitting trials that were preceded by 45 min of either quiet rest (REST) or a single bout of continuous treadmill exercise (65% maximal oxygen consumption) (EX). Superficial femoral artery FMD, plasma glucose, malondialdehyde (MDA), ET-1, arginine (ARG) and its related metabolites [homoarginine (HA), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)] were assessed at baseline, 1 h following EX (or REST) (0 h), and at 1 h intervals during 3 h of uninterrupted sitting. Data were analyzed using repeated measures ANOVA., Results: During REST, femoral artery FMD declined from baseline (2.6 ± 1.8%) at 1, 2, and 3 h of sitting and resting shear rate decreased at 3 h. In contrast, when sitting was preceded by EX, femoral artery FMD (2.7 ± 2.0%) and resting shear rate responses were unaffected. No between trial differences were detected for plasma glucose, MDA, ET-1, ARG, HA, ADMA, or SDMA., Conclusion: Prior aerobic exercise prevented the decline in femoral artery FMD that is otherwise induced by prolonged sitting independent of changes in oxidative stress, ET-1, and NO status.

Objective: To investigate the levels of endothelial constricting and dilating mediators in preterm infants with hypoxic-ischaemic encephalopathy and prospectively evaluate the association between levels measured during the perinatal period and the diagnosis of neurodevelopmental disorders at 3 years of age., Methods: This regional observational cohort study was conducted at the Azerbaijan Medical University, Baku, Azerbaijan, from November 2011 to January 2013, and comprised very-low-birth-weight infants admitted to the intensive care unit during the perinatal period. Blood concentrations of nitric oxide, endothelin-1 and endothelial nitric oxide synthase were measured on days 1-3 and 5-7 of the neonatal period. Concentrations of neuron-specific enolase and antibodies against N-methyl-D-aspartate glutamate receptors were measured in peripheral blood samples for detection of brain damage in the early neonatal period of life. The infants were divided in 3 different groups: those diagnosed with moderate-to-severe neurodevelopmental disorders or cerebral palsy were included in the first group; those with mild neurologic changes were in the second group; and children without evidence of neurological impairment were in the third group. The fourth group comprised controls. SPSS 20 was used for data analysis., Results: Of the 62 participants, there were 8(12.9%) in the first group, 20(32.3%) in second, 14(22.6%) in third and 20(32.3%) in the control group. The activity of endothelial nitric oxide synthase was reduced and nitric oxide concentrations were increased in the first group compared to those in the third group (p<0.05). Deep endothelial nitric oxide synthase depression and insufficient endothelin-1 synthesis were associated with diagnosis in the first group (p<0.05). No differences in concentrations of neuron-specific enolase and NR2 antibodies were identified among infants with and without a subsequent diagnosis of neurodevelopmental disorders (p>0.05)., Conclusions: The association between depressed endothelial nitric oxide synthase activation and insufficient endothelin-1 synthesis in the early days of life of very-low-birth-weight infants might be one of the causes of more serious and irreversible injury of brain tissue.

South Africans are at high risk for developing cardiovascular disease. Endothelin-1 is known for its vasoconstrictive properties and its ability to contribute to vascular structural changes. In this study we investigated the association of change in endothelin-1 levels and change in markers implicated in vascular remodelling after 3 years. Serum endothelin-1 levels and markers of vascular remodelling such as carotid intima-media thickness, carotid cross-sectional wall area (CSWA) and arterial compliance were measured. Participants were divided into two groups according to an increase (n=185) and a decrease (n=152) in plasma endothelin-1 levels after 3 years. In partial regression analysis, the extent of endothelin-1 increase correlated positively with a change in pulse pressure and inversely with the change in arterial compliance in the group with increased endothelin-1 levels after 3 years. In the group with decreased endothelin-1 levels, the extent of decreased endothelin-1 correlated inversely with a change in CSWA. In multiple regression analysis, after splitting for race, the increase in endothelin-1 levels associated positively with the change in pulse pressure (Adj. R 2 =0.092; β=0.278; P=0.036) in the black participants only. In conclusion, with increased endothelin-1 levels after 3 years, the positive association between endothelin-1 and pulse pressure suggest subclinical haemodynamic changes with potential premature onset of cardiovascular disease in the black participants.

Only one in ten patients survives cardiac arrest (CA), underscoring the need to improve CA management. Isoflurane has shown cardio- and neuroprotective effects in animal models of ischemia-reperfusion injury. Therefore, the beneficial effect of isoflurane should be tested in an experimental CA model. We hypothesize that isoflurane anesthesia improves short-term outcome following resuscitation from CA compared with a subcutaneous fentanyl/fluanisone/midazolam anesthesia. Male Sprague-Dawley rats were randomized to anesthesia with isoflurane ( n = 11) or fentanyl/fluanisone/midazolam ( n = 11). After 10 min of asphyxial CA, animals were resuscitated by mechanical chest compressions, ventilations, and epinephrine and observed for 30 min. Hemodynamics, including coronary perfusion pressure, systemic O 2 consumption, and arterial blood gases, were recorded throughout the study. Plasma samples for endothelin-1 and cathecolamines were drawn before and after CA. Compared with fentanyl/fluanisone/midazolam anesthesia, isoflurane resulted in a shorter time to return of spontaneous circulation (ROSC), less use of epinephrine, increased coronary perfusion pressure during cardiopulmonary resusitation, higher mean arterial pressure post-ROSC, increased plasma levels of endothelin-1, and decreased levels of epinephrine. The choice of anesthesia did not affect ROSC rate or systemic O 2 consumption. Isoflurane reduces time to ROSC, increases coronary perfusion pressure, and improves hemodynamic function, all of which are important parameters in CA models. NEW & NOTEWORTHY The preconditioning effect of volatile anesthetics in studies of ischemia-reperfusion injury has been demonstrated in several studies. This study shows the importance of anesthesia in experimental cardiac arrest studies as isoflurane raised coronary perfusion pressure during resuscitation, reduced time to return of spontaneous circulation, and increased arterial blood pressure in the post-cardiac arrest period. These effects on key outcome measures in cardiac arrest research are important in the interpretation of results from animal studies., (Copyright © 2017 the American Physiological Society.)

Background: Hepatopulmonary syndrome (HPS) is characterized by oxygen desaturation and increased intrapulmonary shunting formation in cirrhosis. Due to an unclarified mechanism, there is still no effective therapy except liver transplantation. Recent studies revealed that pulmonary angiogenesis may participate in pathogenesis, in which nitric oxide (NO) and vascular endothelial growth factor (VEGF) play roles. Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, exerts anti-angiogenesis effect. However, whether pioglitazone influences pulmonary angiogenesis, shunting and HPS remains unexplored., Methods: Cirrhosis with HPS was induced in Spraque-Dawley rats with common bile duct ligation (CBDL). Pioglitazone (10 mg/kg/day, oral gavage) or vehicle was administered from 8th to 28th day post CBDL. On the 28th day, the mortality rate, hemodynamic parameters, concentrations of plasma glucose and liver biochemistry parameters, and arterial blood gas data were evaluated. Lungs were dissected for protein expression analyses. In another series, intrapulmonary shunting degree was determined by color microsphere method in paralleled groups., Results: The survival rates were similar in HPS rats with or without pioglitazone administration. Pioglitazone did not influence the hemodynamic parameters, glucose and liver biochemistry levels, oxygen saturation and alveolar arterial gradient, but significantly down-regulated pulmonary VEGF protein expression, endothelial NO synthase (eNOS) activation, and decreased intrapulmonary shunts. Pioglitazone significantly decreased intrapulmonary shunts as compared with the vehicle (18.1 ± 4.5 vs. 9.8 ± 3.6, p = 0.015)., Conclusion: Pioglitazone down-regulated VEGF, eNOS and decreased intrapulmonary shunts without improving oxygenation. The current finding suggests a multifactorial mechanism of HPS that could not be successfully overcome merely by pioglitazone-induced anti-angiogenesis and shunting reduction., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Endothelin-1, a marker of endothelial dysfunction, is a potent vasoconstrictor released by endothelial cells and an important regulator of renal physiology. It is not known whether elevated serum levels of endothelin-1 indicate future risk of kidney disease in the general population. In participants in the Jackson Heart Study, a community-based observational study of cardiovascular risk in black adults, we measured serum endothelin-1 level at baseline (2000-2004; n =3538). We defined incident CKD as eGFR<60 ml/min per 1.73 m 2 and ≥30% eGFR decline at the third visit (2009-2013) relative to baseline among those participants with baseline eGFR ≥60 ml/min per 1.73 m 2 At baseline, mean age was 55 years old, 37% of participants were men, and mean eGFR was 94 ml/min per 1.73 m 2 Over a median follow-up of 8 years, 228 (6.4%) cases of incident CKD occurred in participants. Participants with baseline endothelin-1 levels in higher quartiles had a greater incidence of CKD in the fully adjusted model (odds ratio for fourth versus first quartile, 1.81; 95% confidence interval, 1.11 to 2.96; P trend =0.04). Endothelin-1 positively associated with all-cause mortality (hazard ratio for fourth versus first quartile, 1.64; 95% confidence interval, 1.24 to 2.16; P trend <0.001). In conclusion, higher baseline serum endothelin-1 levels associated with incident CKD and all-cause mortality during follow-up in this general population sample of blacks., (Copyright © 2017 by the American Society of Nephrology.)

Background and Purpose: 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., Experimental Approach: 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., Key Results: 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 ET A receptors and PAR2 was enhanced in Tsk mice. Antagonism of PAR2 potentiated vascular effects of ET-1, whereas antagonism of ET A 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., Conclusions and Implications: 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., Linked Articles: 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., (© 2016 The British Pharmacological Society.)

Introduction: Stent thrombosis (ST) is a rare but catastrophic complication of percutaneous coronary intervention, leading to poor prognosis. Endothelin-1 (ET-1) plays an important role in endothelial dysfunction and thrombogenesis. However, the impact of big ET-1 level on ST in patients with coronary stenting is unknown. We aimed to evaluate big ET-1 level as a potential predictor of ST in patients undergoing percutaneous coronary intervention., Materials and Methods: From January 2013 to December 2013, 8106 consecutive patients underwent successful coronary stent implantation and were prospectively enrolled in this study. Patients were stratified into three groups based on plasma big ET-1 level at admission., Results: The incidence of definite and probable ST at 2years postoperatively was 0.84%; ST incidence was lowest in the low big ET-1 group (0.56%), highest in the high big ET-1 group (1.48%), and intermediate in the medium big ET-1 group (0.74%, log-rank p=0.001). Compared with the low big ET-1 group, the multivariate-adjusted hazard ratio (HR) for ST in the high big ET-1 group was 2.06 (95% confidence interval (CI) 1.14-3.73, p=0.017). In subgroup analyses, high big ET-1 level was independently associated with ST in patients with acute coronary syndrome (HR 2.29, 95% CI 1.03-5.06, p=0.041), but not in those with stable coronary artery disease (p=0.331), and tended to be associated with older age., Conclusions: Plasma big ET-1 level is a valuable independent predictor of ST in patients with coronary stents, especially in the acute coronary syndrome population., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Considering the role of endothelin-1 (ET-1) in tissue remodeling and fibrosis during the development of scleroderma as well as the effect of α-Klotho in pathogenesis of calcinosis and/or endothelial cell injury and its correlation with severity of disease, this study aimed to evaluate serum ET-1, α-Klotho and 25(OH) vitamin D levels in patients with limited and diffuse scleroderma compared to healthy subjects. In this cross-sectional study, 60 scleroderma patients according to the ACR/EULAR 2013 criteria and 60 age- and sex-matched healthy controls were included. In patients, clinical examination was performed and Medsger severity scale was assessed. Serum ET-1, soluble α-Klotho and 25(OH)D 3 levels were measured using ELISA kits. The mean ± SD age of patients and controls was 46.2 ± 9.6 and 47.2 ± 7.0 years, respectively. Compared to healthy controls, serum ET-1 was significantly higher in SSc patients (p = 0.001); whilst serum α-Klotho and 25(OH)D 3 were significantly lower in patients (p = 0.001). The most common organs involved in patients were skin, lung, peripheral vascular and gastrointestinal system and the severity of involvement was mainly mild and/or moderate. There were no significant differences in serum ET-1 and α-Klotho levels according to the severity of different organ involvement (p > 0.05). There was no significant correlation between presence or absence of calcinosis and negative or positivity of auto-antibodies with ET-1, α-Klotho and 25(OH)D 3 levels. Although our study revealed higher serum ET-1 and lower serum α-Klotho levels in SSc patients compared to healthy controls, there were not any significant correlations between their serum levels with severity of organ involvement.

Background: Among septic patients admitted to the intensive care unit (ICU), early recognition of those with the highest risk of death is of paramount importance. We evaluated the prognostic value of Procalcitonin (PCT), mid regional-proadrenomedullin (MR-proADM), copeptine and CT-proendothelin 1 (CT-ProET 1) concentrations., Methods: This was a prospective cohort study, which included 173 septic patient admitted to one ICU. Blood samples for biomarker measurements were obtained upon admission and on day 5. The predictive value of each biomarker regarding the risk of death at day 28 was assessed. The fluid balance was evaluated from admission to day 5., Results: All cause ICU mortality was 36.4%. All the biomarkers except CT-ProET-1 were significantly more elevated in the non-survivors than in the survivors upon day 1. This was especially true for MR-proADM (8.6 [5.9] vs. 4.4 [3.9] nmol/L; P < 0.0001) and for the CT-proET-1/MR-proADM ratio (52.9 [22.4] vs. 31.3 [26.6] arbitrary units; P < 0.0001). The best AUROCC values on day 1 were obtained with MR-ProADM and the CT-proET-1/MR-proADM ratio as well (0.75 [0.67-0.85] and 0.82 [0.75-0.89]; 95% CI, respectively). An improved accuracy was achieved on day 5. Moreover, MR-ProADM baseline levels and fluid balance over the 5-day period following ICU admission were strongly correlated (Rho = 0.41; P < 0.001)., Conclusions: In patients admitted to the ICU with sepsis, MR-ProADM on admission was the best predictor of short-term clinical outcome if compared with others. This could be related to its ability to predict fluid sequestration.

Background: Cardiac remodeling is one of major pathological process in hypertrophic cardiomyopathy (HCM). Endothelin-1 has been linked to cardiac remodeling. Big endothelin-1 is the precursor of endothelin-1., Methods: A total of 245 patients with HCM were enrolled from 1999 to 2011 and partitioned to low, middle and high level groups according to their plasma big endothelin-1 levels., Results: At baseline, significant associations were found between high level of big endothelin-1 and left atrium size, heart function and atrial fibrillation. Big endothelin-1 was positively correlated with N-terminal B-type natriuretic peptide (r=0.291, p<0.001) and late gadolinium enhancement (LGE) on magnetic resonance imaging (r=0.222, p=0.016). During a follow-up of 3 (range, 2-5) years, big endothelin-1 level was positively associated with the risks of all-cause mortality, cardiovascular death and progression to NYHA class 3 or 4 (p=0.020, 0.044 and 0.032, respectively). The rate of above events in the highest tertile were 18.1%, 15.7%, 24.2%, respectively. After adjusting for multiple factors related to survival and cardiac function, the significance remained in the association of big endothelin-1 with the risk of all-cause mortality (hazard ratio (HR)=4.94, 95% confidence interval (CI) 1.07-22.88; p=0.041) and progression to NYHA class 3 or 4 (HR=4.10, 95%CI 1.32-12.75, p=0.015)., Conclusion: Our study showed that high level of plasma big endothelin-1 predicted prognosis for patients with HCM and it can be added to the marker panel in stratifying HCM patients for giving treatment priority to those at high risk., (Copyright © 2017. Published by Elsevier B.V.)

Background: The relation between arrhythmias and stress is known. The aim of our current study was to elucidate whether plasma levels of previously described stress parameters are altered in highly symptomatic patients with atrial fibrillation (AF) per se and in patients undergoing ablation therapy by pulmonary vein isolation (PVI)., Methods: 96 patients with AF undergoing PVI were recruited. Plasma levels of Endothelin-1 (ET-1), MCP-1 and Chromogranin-A (CGA) were measured before and three months after ablation completed with clinical follow-up with respect to AF recurrence. Additionally, we examined 40 healthy age- and sex-matched volunteers as a reference., Results: Symptomatic AF patients showed increased levels of ET-1 compared to healthy controls (2.62pg/ml vs. 1.57pg/ml; p<0.01). Baseline levels of ET-1 were higher in patients presenting with AF after PVI (2.96pg/ml vs. 2.57pg/ml;p = 0.02). The temporal comparison revealed decreased ET-1 levels in patients without (2.57pg/ml vs. 2.33pg/ml; p<0.01) and unchanged ET-1 levels in patients with AF after PVI. Baseline MCP-1 was increased in AF patients vs. controls (268pg/ml vs. 227 pg/ml; p = 0.03). Both groups, with and without AF after PVI, showed an increase of MCP-1 compared to baseline (268pg/ml vs. 349pg/ml;p<0.01; 281pg/ml vs. 355pg/ml;p = 0.03). CGA was lower in AF patients compared to healthy controls (13.8ng/ml vs. 25.6ng/ml;p<0.01). Over time patients without AF after PVI showed an increase of CGA (14.2ng/ml vs. 20.7ng/ml;p<0.01). No change was observed in patients with AF after PVI., Conclusion: Our study demonstrated dysregulated levels of ET-1, MCP-1 and CGA in symptomatic AF patients. We could demonstrate an association between ET-1 to presence or absence of AF. Furthermore, we could show that a decrease of ET-1 as well as an increase of CGA after PVI, representing a trend towards control cohort levels, were both associated with restoration of sinus rhythm. These results provide new insights into the role of stress-related biomarkers in AF and AF treatment by ablation therapy.

New effective treatments are needed to improve outcomes for multiple myeloma (MM) patients. Receptors with restricted expression on plasma cells (PCs) represent attractive new therapeutic targets. The endothelin-1 (EDN1) axis, consisting of EDN1 acting through EDN-receptor A (EDNRA) and B (EDNRB), was previously shown to be overexpressed in several tumours, including MM. However, there is incomplete understanding of how EDN1 axis regulates MM growth and response to therapy. Besides EDNRA, the majority of MM cell lines and primary malignant PCs express high levels of EDNRB and release EDN1. Similarly, bone-marrow microenvironment cells also secrete EDN1. Investigating the extent of epigenetic dysregulation of EDNRB gene in MM, we found that hypermethylation of EDNRB promoter and subsequent down-regulation of EDNRB gene was observed in PCs or B lymphocytes from healthy donors compared to EDNRB-expressing malignant PCs. Pharmacological blockade with the dual EDN1 receptor antagonist bosentan decreased cell viability and MAPK activation of U266 and RPMI-8226 cells. Interestingly, the combination of bosentan and the proteasome inhibitor bortezomib, currently approved for MM treatment, resulted in synergistic cytotoxic effects. Overall, our data has uncovered EDN1-mediated autocrine and paracrine mechanisms that regulate malignant PCs growth and drug response, and support EDN1 receptors as new therapeutic targets in MM., (© 2017 John Wiley & Sons Ltd.)

Background: Contrast-induced acute kidney injury (CI-AKI) is one of the most serious complications in patients who undergo percutaneous coronary intervention (PCI), especially in those with acute coronary syndrome. It has been shown that inflammation may play an important role in the pathophysiology of CI-AKI., Hypothesis: Inflammatory factors may play a predominant role in the prediction of CI-AKI in patients who undergo emergency PCI., Methods: Patients who underwent emergency PCI from 2013 to 2015 were consecutively enrolled and were divided into CI-AKI and non-CI-AKI groups. Logistic analysis was used to identify the risk factors of CI-AKI. Receiver operator characteristic curve analysis was performed to evaluate the area under the curve (AUC) and to establish the optimal cutoff., Results: A total of 1061 patients were included, and the CI-AKI rate was 5.47% (58/1061). Logistic analysis showed that the white blood cell (WBC) count (odds ratio [OR]: 1.103, 95% confidence interval [CI]: 1.018-1.195, P = 0.016), neutrophil (N) count (OR: 1.134, 95% CI: 1.045-1.232, P = 0.003), neutrophil to lymphocyte ratio (NLR) (OR: 1.105, 95% CI: 1.044-1.169, P = 0.001), C-reactive protein (CRP) level (OR: 1.006, 95% CI: 1.001-1.011, P = 0.020), high-sensitivity C-reactive protein (hs-CRP) level (OR: 1.099, 95% CI: 1.020-1.184, P = 0.013), and big endothelin-1 (ET-1) level (OR: 4.030, 95% CI: 1.989-8.165, P < 0.001) were all significant predictors for CI-AKI, as was the left ventricular ejection fraction and diuretic administration. The AUC of the big ET-1 level was the highest (0.793, 95% CI: 0.733-0.853), followed by the NLR (0.708, 95% CI: 0.641-0.774), hs-CRP level (0.705, 95% CI: 0.627-0.782), CRP level (0.684, 95% CI: 0.607-0.761), N count (0.655, 95% CI: 0.584-0.726), WBC count (0.620, 95% CI: 0.544-0.695), and erythrocyte sedimentation rate (0.611, 95% CI: 0.527-0.695)., Conclusions: The WBC count, N count, NLR, CRP level, hs-CRP level, and big ET-1 level are all associated with an increased risk of CI-AKI, and among which, the big ET-1 level, NLR, and the hs-CRP level might have high predictive value for CI-AKI after an emergency PCI., (© 2017 Wiley Periodicals, Inc.)

Objective: To investigate the role of hypoxia-inducible factor-1α and its target genes in hypoxic pulmonary hypertension in neonates., Patients and Methods: A total of 117 newborns were selected and divided into two groups for clinical experiments: 85 cases in the hypoxic pulmonary hypertension (HPH) group, including mild, moderate and severe subgroups, and 32 cases in the case-control group. ELISA was used to detect the serum HIF-1α, endothelin-1 (ET-1) and adrenomedullin (ADM) levels, and echocardiography was used to detect the dynamic changes in pulmonary artery systolic pressure (PASP), right ventricular ejection fraction (RVEF), tricuspid E peak and A peak ratio (E/A) and right ventricular Tei index., Results: The average PASP level of the HPH group was significantly higher than that of the control group at 1 d and 3 d after birth (p < 0.05). The average PASP level was still higher in the severe HPH group than that in the control group at 7 d after birth, while the average levels in the mild and moderate HPH groups recovered to the normal. Compared with those in control group, RVEF and E/A of the tricuspid valve were decreased significantly in severe HPH patients (p < 0.05). The Tei indexes of the right ventricle were significantly higher in the mild, moderate and severe HPH groups than those in control group and the right ventricular Tei index was positively correlated with PASP. The levels of serum ADM, HHH-1α and ET-1 in all the three HPH subgroups were significantly higher than those in the control group at 1 d after birth and showed positive correlations with PASP (p < 0.05), except that serum ADM in mild HPH showed no obvious difference from the control group. The levels of serum HIF-1α and ADM in the severe HPH group and the ET-1 levels in the moderate and severe groups were increased significantly at 3 d after birth (p < 0.05)., Conclusions: The PASP level in neonates with HPH is related to the serum HIF-1α, ET-1 and ADM levels, indicating that hypoxia can increase the level of HIF-1α, which in turn will enhance the expression of downstream target genes ET-1 and ADM, further leading to pulmonary hypertension. The right ventricular Tei index can be used to sensitively detect right ventricular dysfunction of mild, moderate and severe HPH groups.