Analysis of changes in plasma endothelin-1 concentrations in patients with acute respiratory distress syndrome / 中华麻醉学杂志

Objective:To analyze the changes in plasma endothelin-1 (ET-1) concentrations in the patients with acute respiratory distress syndrome (ARDS).Methods:Fourteen patients with ARDS induced by trauma, 8 males and 6 females, aged 19-80 yr, were studied. The severity of ARDS was graded according to the Berlin definition of ARDS after admission to intensive care unit (ICU). Venous blood samples were obtained on 1st, 3rd and 5th days after admission to ICU, the plasma ET-1 concentrations were measured by radioimmunoassay, the pulmonary vascular permeability index (PVPI) was determined by PiCCO technique, and multiple organ dysfunction (MOD) score and lung injury score (LIS) were assessed. Spearman correlation of plasma ET-1 concentrations with MOD score, LIS and PVPI was analyzed.Results:MOD score, LIS, PVPI and plasma ET-1 concentrations were significantly decreased in mild ARDS patients ( n=5) as compared with moderate ARDS patients ( n=9, P<0.05). The plasma ET-1 concentration was positively correlated with MOD score, LIS and PVPI ( r=0.69, 0.76, 0.62, P<0.001). Conclusions:Plasma ET-1 concentrations can reflect the pulmonary vascular permeability and even the severity of the disease in the early stage of ARDS, so it is necessary to carry out dynamic monitoring in the patients.

Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease

Introduction: The female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males. Aim: We aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ETA) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD). Methods: We compared prevalence of ET-1 gene (Lys198Asn) and ETA gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls. Results: The presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p ¼0.007 and OR 2.39; p ¼0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p ¼0.047 and OR 2.26; p ¼0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p ¼0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p ¼0.018) were independent predictors of development of PH in females.

Upregulation of ppET-1/ETBR/eNOS mRNA Expression After Calcitriol Treatment in Chronic Kidney Diseases Model in Rats

@#Introduction: Myofibroblast formation in the interstitial area is the hallmark of chronic kidney disease (CKD). Endothelin signalling has been known to play role in physiology and pathophysiology in the kidney. Vitamin D has a reno-protective effect through inhibiting inflammation and fibrosis. However, the interaction between vitamin D and endothelin signalling in the CKD model has not been elucidated yet. Therefore, we aimed to check the difference impact of endothelin (ET) receptor in CKD. Methods: Sprague Dawley rats (3-months-old, 150-250grams) underwent 5/6 subtotal nephrectomy (SN) to induce CKD. Then, it was divided into 4 groups (each contains 6 rats): sham operation (SO), 5/6 subtotal nephrectomy (SN), calcitriol groups (0.01µg/100grBW/day (SN-D1), and 0.05µg/100grBW/day (SN-D2). Calcitriol was administered for 14 days after the surgery. The Sham Operation (SO) group was injected with NaCl. At the specified date, the rats were sacrificed and the kidneys were harvested. Fibrosis was quantified based on Sirius Red staining. Immunostaining was done for localizing fibroblast (PDGFRβ). The mRNA expressions of prepro-ET-1, endothelin receptor A (ETAR), endothelin receptor B (ETBR), and endothelial nitrite oxide synthase (eNOS) were quantified using reverse-transcriptase PCR (RT-PCR). Results: The CKD promotes an elevation of prepro-ET-1, ETBR, and eNOS, and reduction of ETAR (p<0.05) mRNA expression compared to the SO group. Administration of calcitriol (SN-D1 and SN-D2) showed the vice versa effects. However, only SN-D2 group consistently showed statistically significant differences whenever compared to either SO or SN groups. Conclusion: Calcitriol might attenuate interstitial fibrosis in CKD model via ET-1/eNOS signalling.

Involvement of ET-1/eNOS in the ameliorating effect of electroacupuncture on cardiac dysfunction in rats with spontaneously hypertensive / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function of ventriculus sinister in rats with spontaneously hypertensive (SHR), and to explore the mediation effect of endothelin-1 (ET-1)/endothelial nitric oxide synthase (eNOS).@*METHODS@#Six 12-week-old male Wistar Kyoto (WKY) rats were taken as the normal group. Eighteen 12-week-old SHR were randomly divided into a model group, an EA group and a sham EA group, 6 rats in each group. The rats in the EA group were treated with EA (disperse-dense wave, 2 Hz/15 Hz in frequency, 1 mA in current intensity) at "Neiguan" (PC 6), 30 min each time, once a day for 8 weeks. The rats in the sham EA group were treated with superficial needling at "Neiguan" (PC 6) with no electrical stimulation applied. After treatment, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were tested by echocardiographic analysis. The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), heart rate (HR), the maximum rate of increase/decrease of left ventricular pressure (±dp/dtmax) were detected. The serum content of ET-1 was detected by ELISA. Western blot was used to evaluate the expression of ETAR, eNOS in myocardial tissue of left ventricular.@*RESULTS@#Compared with the normal group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were decreased (P<0.01, P<0.05), while LVSP, LVEDP, +dp/dtmax and -dp/dtmax were increased (P<0.01) in the model group. Compared with the model group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were increased (P<0.01, P<0.05), and LVSP and LVEDP were decreased (P<0.01) in the EA group. Compared with the normal group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were increased (P<0.01), whereas expression of eNOS was decreased (P<0.01) in the model group. Compared with the model group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were decreased (P<0.05), whereas expression of eNOS was increased (P<0.05) in the EA group.@*CONCLUSION@#EA intervention may alleviate hypertensive cardiac function damage by up-regulating the expression of eNOS protein in myocardial tissue, down-regulating the serum content of ET-1 and the expression of ETAR protein in myocardial tissue.

Efficacy of triamcinolone acetonide injection behind the eyeball in the treatment of Purtscher disease and its effect on vision, inflammatory factors, nitric oxide and endothelin-1 of aqueous fluid / 中国医师进修杂志

Objective:To investigate the efficacy of triamcinolone acetonide injection behind the eyeball in the treatment of Purtscher disease and its effects on vision, inflammatory factors, nitric oxide (NO) and endothelin-1 (ET-1) of aqueous fluid.Methods:A total of 64 patients with Purtscher disease admitted to First People′s Hospital of Lanzhou City from January 2016 to January 2020 were selected and divided into two groups by random number table, with 32 cases in each group. The control group was given conventional treatment, and the observation group was injected with triamcinolone acetonide behind the eyeball on this basis. The total effective rate after 6 weeks of treatment, the best corrected visual acuity and hemodynamic indicators peak flow velocity (V max), end-diastolic flow velocity (V min), resistance index (RI) of ophthalmic artery and central retinal artery during systole, aqueous humor inflammatory factors tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-2, IL-6, NO, ET-1, and adverse reactions after 3 and 6 weeks of treatment were compared between the two groups. Results:After 6 weeks of treatment, the total effective rate in the observation group was higher than that in the control group: 96.9% (31/32) vs. 75.0% (24/32), and the difference was statistically significant ( χ2 = 4.655, P<0.05). After 3, 6 weeks of treatment, the best corrected visual acuity in the observation group was higher than that in the control group: 0.44 ± 0.13 vs. 0.35 ± 0.12, 0.88 ± 0.16 vs. 0.62 ± 0.15, and the difference was statistically significant ( P<0.05). After 3, 6 weeks of treatment, the V max and V min of the ophthalmic artery and central retinal artery in the observation group were higher than those in the control group: after 3 weeks of treatment: (29.42 ± 0.93) cm/s vs. (28.65 ± 0.90) cm/s, (8.04 ± 1.08) cm/s vs. (6.95 ± 1.12) cm/s, (8.42 ± 1.21) cm/s vs. (8.39 ± 1.19) cm/s, (4.05 ± 0.61) cm/s vs.(3.58 ± 0.57) cm/s; after 6 weeks of treatment: (31.72 ± 1.03) cm/s vs. (29.58 ± 0.95) cm/s, (9.81 ± 1.06) cm/s vs. (7.78 ± 1.15) cm/s, (12.01 ± 1.23) cm/s vs. (10.82 ± 1.07) cm/s, (4.65 ± 0.47) cm/s vs. (4.02 ± 0.36) cm/s; the RI of the ophthalmic artery and central retinal artery in the observation group were lower than those in the control group: after 3 weeks of treatment: 0.76 ± 0.06 vs. 0.80 ± 0.05, 0.70 ± 0.03 vs. 0.76 ± 0.04; after 6 weeks of treatment: 0.71 ± 0.05 vs.0.75 ± 0.04, 0.68 ± 0.04 vs.0.72 ± 0.03, and the differences were statistically significant ( P<0.05). After 3 and 6 weeks of treatment, the levels of TNF-α, IL-1β, IL-2, IL-6 of aqueous fluid in the observation group werelower than those in the control group: after 3 weeks of treatment: (2.61 ± 0.38) μg/L vs.(4.75 ± 0.41) μg/L, (3.45 ± 0.28) μg/L vs.(6.28 ± 1.05) μg/L, (6.28 ± 0.34) μg/L vs. (9.45 ± 1.14)μg/L, (9.82 ± 1.66) ng/L vs. (12.45 ± 2.31) ng/L; after 6 weeks of treatment: (0.98 ± 0.23) μg/L vs. (1.44 ± 0.27) μg/L, (1.11 ± 0.36) μg/L vs. (1.69 ± 0.38) μg/L, (3.68 ± 1.02) μg/L vs. (5.73 ± 1.15) μg/L, (4.11 ± 1.19) ng/L vs. (7.38 ± 1.06) ng/L, and the differences were statistically significant ( P<0.05). After 3, 6 weeks of treatment, the levels of NO in the observation group washigher than that in the control group: (56.49 ± 9.17) μmol/L vs. (50.22 ± 8.68) μmol/L, (60.18 ± 8.27) μmol/L vs. (53.24 ± 7.96) μmol/L; the levels of ET-1 waslower than that in the control group: (60.77 ± 9.61) ng/L vs. (65.02 ± 10.85) ng/L, (56.59 ± 7.22) ng/L vs. (61.18 ± 6.76) ng/L, and the differences were statistically significant ( P<0.05). The incidence of adverse reactions in the two groups had no statistical significance ( P>0.05). Conclusions:The injection of triamcinolone acetonide behind the eyeball to treat Purtscher disease can improve ocular hemodynamics, inhibit inflammation, improve vascular endothelial function and improve visual acuity. It has significant curative effect and certain safety.

Comparison of intravenous anesthesia between propofol and etomidate in patients undergoing laparoscopic surgery and their effects on plasma nitric oxide and endothelin-1 / 中国医师进修杂志

Objective:To compare the effects of intravenous anesthesia between propofol and etomidate in patients undergoing laparoscopic surgery and their effects on plasma nitric oxide (NO) and endothelin-1 (ET-1).Methods:The clinical data of 80 patients with laparoscopic surgery in Guangrao People′s Hospital from March 2017 to March 2019 were retrospectively analyzed. Among them, 40 cases were given propofol intravenous anesthesia (propofol group), and 40 cases were given etomidate intravenous anesthesia (etomidate group). The anesthetic effect, plasma NO and ET-1 levels, hemodynamic indexes and adverse reactions (muscle spasm, nausea and vomiting, injection site pain, body movement and respiratory depression) were compared between the two groups.Results:The time of consciousness disappearance, tracheal intubation, eye opening, spontaneous breathing and speech response in etomidate group were significantly shorter than those in propofol group: (57.48 ± 2.63) s vs. (86.17 ± 7.41) s, (4.39 ± 2.56) min vs. (6.42 ± 2.58) min, (5.39 ± 2.56) min vs. (9.42 ± 2.58) min, (5.21 ± 1.99) min vs. (8.75 ± 2.54) min and (8.39 ± 2.56) min vs. (8.39 ± 2.56) min, and the differences were statistically significant ( P<0.05). The levels of NO and ET-1 in the etomidate group were significantly lower than those in the propofol group at 0.5, 1.0 and 1.5 h after pneumoperitoneum ( P< 0.05). The levels of systolic blood pressure, diastolic blood pressure and oxygen saturation (SpO 2) in the etomidate group were significantly higher than those in the propofol group: (78.42 ± 4.68) mmHg (1 mmHg = 0.133 kPa) vs. (74.11 ± 6.63) mmHg, (132.86 ± 8.71) mmHg vs. (111.24 ± 3.56) mmHg and 0.982 ± 0.032 vs. 0.953 ± 0.043, and the differences were statistically significant ( P<0.05). The incidence of adverse reactions in the etomidate group was significantly lower than that in the propofol group: 17.5% (7/40) vs. 47.5% (19/40), P<0.05. Conclusions:Compared with propofol intravenous anesthesia, etomidate intravenous anesthesia in laparoscopic surgery patients has more stable hemodynamics and better anesthetic effect. It can effectively inhibit the release of NO and ET-1, and has higher safety.

Serum endothelin-1 level in children with osteosarcoma and its correlation with lung metastasis / 中华实用儿科临床杂志

Objective:To investigate the serum levels, diagnosis and prognosis value of endothelin-1(ET-1) in children suffering from lung metastasis of osteosarcoma.Methods:A total of 84 children with osteosarcoma, 67 children with lung metastasis of osteosarcoma and 35 healthy people from January 1, 2013 to January 1, 2018 in Second People′s Hospital of Nanyang were retrospectively included.The serum level of ET-1 was measured by performing enzyme linked immunosorbent assay(ELISA) methods and the influencing factors of serum ET-1 levels in children with lung metastasis of osteosarcoma were conducted by Logistic regression analysis.The clinical value of ET-1 in the prediction of the incidence of lung metastasis in children with osteosarcoma was analyzed by receiver operating characteristic (ROC) curve.Forty-five children with lung metastasis of osteosarcoma were followed up for 18 months and the prognosis value of serum ET-1 levels in children with lung metastasis of osteosarcoma was evaluated by Kaplan-Meier survival analysis. Results:The serum ET-1 level in children with lung metastasis of osteosarcoma was 97.23 (65.13, 134.98) ng/L and significantly higher than osteosarcoma group 60.21 (43.12, 74.63) ng/L and healthy control group 34.45 (12.01, 63.03) ng/L, respectively ( Z=-5.671, -4.92, all P<0.05), with significant differences. Logistic regression analysis proved that lung bilateral involvement ( OR=3.449), numbers of lung metastases (more than 3)( OR=3.449), average diameter of lung metastases (more than 5 cm) ( OR=6.501) and extrapulmonary metastasis ( OR=4.369) were independent risk factors for elevated serum ET-1 levels in children developing lung metastasis of osteosarcoma.The predictive value of ET-1 in the incidence of lung metastasis in children with osteosarcoma was significant (area under ROC curve: 0.841). When the cut-off value was 94.27 ng/L, the sensitivity and specificity were 88.5% and 92.6%, respectively.Survival analysis revealed that higher levels of ET-1 was correlated with poor prognosis ( OR=3.287, 95% CI: 1.119-9.547). Conclusions:The serum levels of ET-1 in children with lung metastasis of osteosarcoma are significantly elevated.ET-1 is a serological marker for the differential diagnosis of lung metastasis of osteosarcoma.Moreover, the higher levels of ET-1 are correlated with poor prognosis in children with lung metastasis of osteosarcoma.

Endothelin-1 gene Lys198Asn polymorphism and ischemic stroke / 国际脑血管病杂志

Endothelin (ET) is a potent vasoconstrictor peptide produced by endothelial cells, which is closely associated with vascular endothelial dysfunction and cardio-cerebrovascular diseases. Recent studies have shown that ET-1 gene Lys198Asn polymorphism can be used as a new biomarker of cerebrovascular diseases. This article reviews the research progress on the relationship between the gene polymorphism and susceptibility to ischemic stroke, and discusses its clinical significance.

Effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome with different glucose tolerance status / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome (PCOS) with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT).@*METHODS@#A total of 140 patients with PCOS were divided into an IGT group (70 cases, 11 dropped off) and a NGT group (70 cases, 9 cases dropped off). The patients in the two groups were treated with full-cycle acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Tianshu (ST 25), etc. once every other day, 3 times a week, for 3 months. Before and after treatment, TCM symptom score, insulin resistance index [including fasting plasma glucose (FPG), 2-hour blood glucose (2hPG), fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)] and vascular endothelial related factors [including asymmetric dimethylarginine (ADMD), endothelin-1 (ET-1), malondialdehyde (MDA), nitric oxide (NO)] were compared between the two groups; in addition, the obese subgroup and non-obese subgroup of the two groups were further compared.@*RESULTS@#Compared before treatment, the TCM symptom scores, ADMD, ET-1 and MDA after treatment were decreased (@*CONCLUSION@#Acupuncture could improve vascular endothelial function in PCOS patients, IGT patients have better efficacy than NGT patients, and obese patients have better efficacy than non-obese patients.

Relationship and risk factors of osteonecrosis of femoral head after internal fixation of femoral neck fracture with serum bone metabolism and vasoactive factors / 中国骨伤

OBJECTIVE@#To study the relationship between osteonecrosis of femoral head after internal fixation of femoral neck fracture and serum bone metabolism, vascular active factors, and analyze the risk factors.@*METHODS@#Total 150 patients with femoral neck fracture who underwent reduction and internal fixation from April 2016 to April 2019 were selected, including 83 males and 67 females. According to whether there was necrosis of femoral head after operation, they were divided into necrosis group(32 cases) and non necrosis group (118 cases). Before operation and 1, 3, 5 days after operation, the serum levels of beta-C terminal cross-linked telopeptides of typeⅠ collagen(β-CTX), N-telopeptide of typeⅠ procollagen(PINP), nitric oxide (NO), Endothelin-1 (ET-1) were measured. The clinical characteristics of the two groups were compared. The risk factors of postoperative femoral head necrosis were analyzed by logistic regression model. The value of serum indexes in predicting postoperative femoral head necrosis was analyzed by ROC curve.@*RESULTS@#There was no significant difference in the levels of serum PINP and β-CTX between necrotic group and non necrotic group before operation and 1, 3 and 5 days after operation(@*CONCLUSION@#The content of serum NO and ET-1 on the first day after operation can predict the necrosis of femoral head.

Association between liver fibrosis progression and endothelin-1/nitric oxide in patients with nonalcoholic fatty liver disease / 临床肝胆病杂志

Objective To investigate whether the progression of liver fibrosis affects endothelial function in patients with nonalcoholic fatty liver disease (NAFLD), and to early identify the warning of cardiovascular diseases caused by endothelial dysfunction by liver fibrosis progression. Methods A total of 280 patients who attended the outpatient service or were hospitalized in Department of Liver Disease, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, from April 2019 to October 2020 were enrolled, and they were diagnosed with fatty liver disease by ultrasound and met the diagnostic criteria for NAFLD. General information and related serological markers were collected and recorded. FibroTouch technique was performed for the NAFLD patients diagnosed by ultrasound to record their fat attenuation parameter (FAP) and liver stiffness measurement (LSM), and according to LSM, the patients were divided into non-progressive fibrosis group (239 patients with LSM 0.05). Further analysis of the correlation of ET-1 and NO with each index showed that ET-1 was not correlated with age, NO, ALT, AST, GGT, total cholesterol, TG, HDL-C, low-density lipoprotein cholesterol (LDL-C), FAP, and BMI ( r s =-0.017, 0.054, -0.067, -0.016, -0.031, 0.004, 0.051, -0.084, -0.030, 0.080, and 0.044, all P > 0.05), and NO was not correlated with age, ET-1, ALT, AST, GGT, total cholesterol, TG, HDL-C, LDL-C, FAP, and BMI ( r s =0.004, 0.054, 0.011, 0.052, 0.004, -0.051, -0.052, -0.012, -0.076, -0.013, and -0.021, all P > 0.05). Conclusion This study shows that liver fibrosis progression in NAFLD has no impact on ET-1 and NO, suggesting that fibrosis progression may have no influence on endothelial function.

Effect of electroacupuncture on choroidal blood flow and the expression of endothelin-1 and its receptor in lens-induced myopic guinea pigs / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To observe the changes of the vessel density of choriocapillaris in lens-induced myopia in guinea pigs, and to explore choroidal endothelin-1(ET-1), endothelin receptor A(ETAR)and receptor B(ETBR)expression changes and the effect of electroacupuncture. <p>METHODS: Fifty-four guinea pigs were randomly divided into normal control(NC), lens-induced myopia(LIM)and LIM+electroacupuncture(LIM+EA). The NC group was fed normally without intervention and the right eye in LIM group and LIM+EA group was coverd with a -6.00D lens to establish a myopia model. At 2 and 4wk, the refraction, axial length and the vessel density of choriocapillaris in groups were measured. The expression and protein content of ET-1, ETAR and ETBR mRNA in groups were detected by the real-time fluorescent quantitative PCR(quantitative polymerase chain reaction, q-PCR), enzyme-linked immunosorbent assay(ELISA)and immunohistochemistry. <p>RESULTS: At 2 and 4wk, compared with the the NC group, refraction and axial length in LIM group and LIM+EA group had significantly increased(all <i>P</i><0.001). Compared with the LIM group, the refraction and axial length in LIM+EA group were decreased(all <i>P</i><0.05). At 2 and 4wk, compared with the NC group,the vessel density of choriocapillaris was decreased(<i>P</i><0.001)and the ET-1, ETAR and ETBR mRNA and protein levels in choroid were increased(all <i>P</i><0.05)in LIM group. At 2 and 4wk, compared with the LIM group,the vessel density of choriocapillaris was decreased(<i>P</i><0.01)and the ET-1, ETAR and ETBR mRNA and protein levels in choroid were increased in LIM+EA group.<p>CONCLUSION:In LIM guinea pigs, the choroidal blood flow decreased with the increased of refraction and axial length, which may affect ET-1 and its receptors through vascular shear force during the development of myopia. At the same time, electroacupuncture can improve choroidal blood flow through neuromodulation and affects the vascular shear stress to down-regulate the content of ET-1 and its receptor to delay the development of myopia.

Role of FAK signaling in chagasic cardiac hypertrophy

Abstract Cardiac hypertrophy and dysfunction are a significant complication of chronic Chagas disease, with heart failure, stroke, and sudden death related to disease progression. Thus, understanding the signaling pathways involved in the chagasic cardiac hypertrophy may provide potential targets for pharmacological therapy. Herein, we investigated the implication of focal adhesion kinase (FAK) signaling pathway in triggering hypertrophic phenotype during acute and chronic T. cruzi infection. C57BL/6 mice infected with T. cruzi (Brazil strain) were evaluated for electrocardiographic (ECG) changes, plasma levels of endothelin-1 (ET-1) and activation of signaling pathways involved in cardiac hypertrophy, including FAK and ERK1/2, as well as expression of hypertrophy marker and components of the extracellular matrix in the different stages of T. cruzi infection (60-210 dpi). Heart dysfunction, evidenced by prolonged PR interval and decrease in heart rates in ECG tracing, was associated with high plasma ET-1 level, extracellular matrix remodeling and FAK signaling activation. Upregulation of both FAK tyrosine 397 (FAK-Y397) and serine 910 (FAK-S910) residues phosphorylation as well as ERK1/2 activation, lead to an enhancement of atrial natriuretic peptide gene expression in chronic infection. Our findings highlight FAK-ERK1/2 signaling as a regulator of cardiac hypertrophy in Trypanosoma cruzi infection. Both mechanical stress, induced by cardiac extracellular matrix (ECM) augment and cardiac overload, and ET-1 stimuli orchestrated FAK signaling activation with subsequent activation of the fetal cardiac gene program in the chronic phase of infection, highlighting FAK as an attractive target for Chagas disease therapy.

Imbalance between Endothelin-1 and eNOS Expression Associates with Tubular Injury in Mice with 5/6 Subtotal Nephrectomy

@#Introduction: Chronic Kidney Diseases (CKD) leads to kidney fibrosis which characterized by tubular injury and atrophy with interstitial fibrosis. Endothelin-1 (ET-1) and endothelial Nitrite Oxide Synthase (eNOS) are known to play role in CKD and kidney fibrosis, although their correlation with tubulo-interstitial injury have not been understood clearly. Methods: 5/6 Subtotal Nephrectomy (SN) was performed in male Swiss Background mice to induce CKD. Sham operation (SO, n=5) procedure was performed on mice as control. The mice were sacrificed in day 7 (1N, n=5) and day 28 (4N, n=5) after operation. We measured creatinine serum to assess renal function. Tubular injury score was quantified based on Periodic-Acid Schiff (PAS) staining. Prepro-ET-1 and eNOS were quantified using RT-PCR. Results: SN_1N and SN_4N groups had significant higher of serum creatinine and tubular injury from SO group. Densitometry analysis of RT-PCR revealed up-regulation of prepro-ET-1 mRNA expression in SN_1N and SN_4N (p<0.05 vs SO). Meanwhile, we found a significant increase of eNOS expression in SN_1N, and then it reduced significantly in SN_4N. We found significant parallel correlation between ET-1 and tubular injury expression (r: 0.768;p<0,05), meanwhile there were insignificant inverse correlation between eNOS and tubular injury (r: -0.354;p>0.05). Conclusion: eNOS might play role as a counterbalance in the up regulation of ET-1 in acute condition after SN. However, it failed in chronic condition. These lead to deterioration of renal function and tubular injury. An imbalance between ET-1 and eNOS expression in chronic CKD model might play role in profound renal damage.

Antioxidant effect of endothelin-1 receptor antagonist protects the rat kidney against chronic injury induced by hypertension and hyperglycemia / Efeito antioxidante de antagonista dos receptores de endotelina-1 protege ratos contra lesão renal crônica induzida por hipertensão e hiperglicemia

ABSTRACT Hypertension and Diabetes mellitus are the two main causes of chronic kidney disease that culminate in the final stage of kidney disease. Since these two risk factors are common and can overlap, new approaches to prevent or treat them are needed. Macitentan (MAC) is a new non-selective antagonist of the endothelin-1 (ET-1) receptor. This study aimed to evaluate the effect of chronic blockade of ET-1 receptor with MAC on the alteration of renal function observed in hypertensive and hyperglycemic animals. Genetically hypertensive rats were divided into control hypertensive (HT-CTL) group, hypertensive and hyperglycemic (HT+DIAB) group, and hypertensive and hyperglycemic group that received 25 mg/kg macitentan (HT-DIAB+MAC25) via gavage for 60 days. Kidney function and parameters associated with oxidative and nitrosative stress were evaluated. Immunohistochemistry for neutrophil gelatinase-associated lipocalin (NGAL), ET-1, and catalase in the renal cortex was performed. The HT+DIAB group showed a decrease in kidney function and an increase in NGAL expression in the renal cortex, as well as an increase in oxidative stress. MAC treatment was associated with attenuated ET-1 and NGAL production and increases in antioxidant defense (catalase expression) and nitric oxide production. In addition, MAC prevented an increase in oxidant injury (as measured by urinary hydroperoxide and lipid peroxidation), thus improving renal function. Our results suggest that the antioxidant effect of the ET-1 receptor antagonist MAC is involved in the improvement of kidney function observed in hypertensive and hyperglycemic rats.

RESUMO Hipertensão e Diabetes Mellitus figuram como as duas principais causas de doença renal crônica que culmina em doença renal terminal. Uma vez que os dois fatores de risco são comuns e podem se sobrepor, novas abordagens preventivas e terapêuticas se fazem necessárias. O macitentan (MAC) é um novo antagonista não-seletivo dos receptores da endotelina-1 (ET-1). O presente estudo teve como objetivo avaliar os efeitos do bloqueio crônico dos receptores da ET-1 com MAC sobre a alteração da função renal em animais hipertensos e hiperglicêmicos. Ratos geneticamente hipertensos foram divididos em grupos com animais hipertensos de controle (HT-CTL), hipertensos e hiperglicêmicos (HT+DIAB) e hipertensos e hiperglicêmicos tratados com 25 mg/kg de macitentan (HT-DIAB+MAC25) via gavagem por 60 dias. Foram avaliados função renal e parâmetros associados ao estresse oxidativo e nitrosativo. Exames de imunoistoquímica foram realizados para lipocalina associada à gelatinase neutrofílica (NGAL), ET-1 e catalase no córtex renal. O grupo HT+DIAB exibiu diminuição da função renal e aumento na expressão de NGAL no córtex renal, bem como estresse oxidativo aumentado. O tratamento com MAC foi associado a atenuação da produção de ET-1 e NGAL e maior ativação das defesas antioxidantes (expressão de catalase) e elevação da produção de óxido nítrico. Além disso, o MAC evitou exacerbação da lesão oxidante (medida por hidroperóxidos urinários e peroxidação lipídica), melhorando assim a função renal. Nossos resultados sugerem que o efeito antioxidante do antagonista dos receptores da ET-1 MAC esteja imbricado no aprimoramento da função renal observada em ratos hipertensos e hiperglicêmicos.

Correlation between erythrocyte immune function and erythropoietin and plasma endothelin-1 in patients with angle-closure glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the correlation between erythrocyte immune function and serum erythropoietin(EPO)and plasma endothelin-1(ET-1)in patients with angle-closure glaucoma.<p>METHODS: Totally 30 patients with angle-closure glaucoma(case group)and 30 normal eyes(control group)were selected from our hospital from June 2017 to October 2017. The erythrocyte immune function, serum EPO and plasma ET-1 levels were measured and compared between the two groups.<p>RESULTS: The rosette rate of erythrocyte C3b receptor in the case group was significantly lower than that in the control group(10.81%±2.01% <i>vs</i> 18.06%±3.44%), the rosette rate of erythrocyte immune complex was significantly higher than that in the control group(17.21%±3.49% <i>vs</i> 11.74%±2.14%), the serum EPO concentration was significantly higher than that in the control group(26.10%±5.22mU/mL <i>vs</i> 22.68%±4.06mU/mL), and the plasma ET-1 concentration was significantly higher than that in the control group(70.85%±7.16ng/L <i>vs</i> 58. 43±5.09ng/L). The rosette rate of erythrocyte C3b receptor in patients with angle-closure glaucoma was positively correlated with serum EPO concentration(<i>r</i>=0.271, <i>P</i><0.05), but not with plasma ET-1 concentration.<p>CONCLUSION: There is a positive correlation between erythrocyte immune function and serum EPO concentration in patients with angle-closure glaucoma.

Mechanism of endothelin-1 mediated the cyclic intermittent hypoxia on carotid body plasticity in rats / 解剖学报

Objective To investigate the potential molecular mechanism of endothelin-1 (ET-1) involved in cyclic intermittent hypoxia (CIH) induced carotid body chemoreceptor plasticity. Methods (1) Animal experiment: 32 male Sprague-Dawley (SD) rats were randomly divided into two groups: Control group (Con) and CIH group (CIH), 16 rats per group. After 21 days of CIH exposure, each group (Con and CIH) was subdivided into 2 groups: Lail vein injection of ET-1 (1 x 10~6 mol/kg body weight) or same volume of saline according to the above dose. After 30 minutes of injection, carotid bodies were collected and Western blotting was used to detect the change of tested proteins. (2) Carotid body organ culture: Rat carotid bodies were isolated and cultured in the incubator, and treated with ET-i (lxlO"4 mol/L) for different times (0 minute, 10 minutes, 60 minutes). The effect of ET-1 on the phosphorylation of p38 mitogen-activated protein l kinase (p38 MAPK) was detected by Western blotting. Results (1) CIH increased the protein level of endothelin receptor A (ET-A)and ET-B in the rat carotid body. (2) Compared with the ET-1 injected Con group, phosphorylated protein kinase A (p-PKA), p-p38 MAPK, phosphorylated Ca2;/calmodulin-dependent protein kinase D (p-CaMK II) and phosphorylated cAMP response element-binding protein (p-CREB) and RhoA protein level were significantly up-regulated in ET-1 injected CIH rats. (3) Application of ET-1 to organ cultured carotid bodies resulted in the elevation of p-p38 MAPK in a time-dependent manner. Conclusion ET-1 may regulate CIH-induced carotid body chemoreflex plasticity through PKA/p38 MAPK/CaMK II/CREIJ and IthoA signaling.

Effect of Modified Erchentang on VEGF,VEGFR2,IL-4,ET-1 in Chronic Obstructive Pulmonary Disease Rats / 中国实验方剂学杂志

Objective: To observe the effects of Erchen on vascular endothelial growth factor (VEGF) and its receptor R2 (VEGFR2), interleukin (IL)-4 and endothelin-1 (ET-1) in rats with chronic obstructive pulmonary disease (COPD). Method: The 50 SD rats were randomly divided into 5 groups, 10 rats in each group, which were normal group, model group, Erchentang low, medium and high dose group (10, 20, 40 g · kg-1 · d-1). COPD rat model was established by smoking combined with lipopolysaccharide (LPS) intratracheal drip. After successful modeling, the treatment group was given intragastric administration, and the normal group and the model group were given intragastric distilled water of equal volume. The pathological changes of pulmonary vessels in rats were observed by light microscopy, and the thickness of pulmonary vascular wall was measured. The concentration of IL-4 in rat serum, bronchoalveolar lavage fluid (BALF) and lung homogenate was measured by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the expression of ET-1 and immunohistochemistry was used to detect the expression of VEGF,VEGFR2 and ET-1 in lung tissue. Result: Compared with normal group, the concentration of IL-4 in serum, BALF and lung homogenate of model group rats decreased significantly (PPPPPPConclusion: Modified Erchentang can alleviate the process of pulmonary inflammation and pulmonary vascular remodeling in COPD rats, and slow down the progress of COPD and its complications by increasing the content of IL-4, inhibiting the expression of VEGF, VEGFR2, ET-1.

CD34, VEGF and endothelin-1 expression in intrahepatic metastasis of hepatocellular carcinoma / 中华普通外科杂志

Objective@#To explore the roles of CD34, VEGF and endothelin-1 in hepatic sinusoid capillarization and the intrahepatic metastasis of hepatocellular carcinoma.@*Methods@#Data of 10 cases of hepatocellular carcinoma without intrahepatic metastasis were compared with those 10 cases of hepatocellular carcinoma with intrahepatic metastasis . Liver cancer tissues and paracancerous tissues were collected, hepatic sinusoidal capillarization was detected by immunohistochemistry, mRNA expression and protein expression of CD34, VEGF and endothelin-1 genes were detected by QPCR, Western blot, and the relationship between gene expression and metastasis of HCC was observed.@*Results@#Hepatic sinusoid capillarization was observed in carcinoma tissues, not in the adjacent tissues, whereas mRNAs and proteins of CD34, VEGF and endothelin-1 were higher in liver cancer tissues than that in the adjacent tissuess. In addition, both mRNA and protein expression levels of these genes were significantly higher in the intrahepatic metastatic liver cancers than those without metastasis (P<0.05).@*Conclusion@#CD34, VEGF and endothelin - 1 may play important roles in intrahepatic metastasis of liver cancer.