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https://www.readbyqxmd.com/read/28429342/assessment-of-serum-endothelin-1-levels-in-rat-appendicitis-model-and-the-effects-of-bosentan
#1
S B Sarsu, K Sahin, H Kilincaslan, S L Mirapoglu, N Buyukpınarbasili, M E Duz, I Aydogdu
OBJECTIVE: In this study, the diagnostic value of serum endothelin-1 (ET-1) levels and the therapeutic effects of bosentan have been investigated in an experimental appendicitis rat model. MATERIALS AND METHODS: Twenty-one male Sprague-Dawley rats were chosen for the study. The rats were allocated into three groups as follows: Group 1 (control, n = 7), Group 2 (appendicitis, n = 7), and Group 3 (bosentan treatment, n = 7). At the 6th hour of the experiment, Groups 1 and 2 received 2 ml saline, and group 3 received 30 mg/kg bosentan intraperitoneally...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28425346/ambrisentan-a-review-of-its-use-in-pulmonary-arterial-hypertension
#2
Belinda N Rivera-Lebron, Michael G Risbano
Pulmonary arterial hypertension (PAH) is a progressive disease defined by an elevation in pulmonary arterial pressure that can lead to right heart failure and death. Ambrisentan is a selective endothelin receptor antagonist approved for the treatment of idiopathic, heritable PAH and connective tissue disease-associated PAH. Ambrisentan has been shown to improve exercise capacity and hemodynamics with an acceptable side-effect profile. It has also proven to be safely used in combination with other PAH-specific medications, especially with phosphodiesterase-5 inhibitors...
April 1, 2017: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/28423608/anthracyclines-suppress-pheochromocytoma-cell-characteristics-including-metastasis-through-inhibition-of-the-hypoxia-signaling-pathway
#3
Ying Pang, Chunzhang Yang, Jan Schovanek, Herui Wang, Petra Bullova, Veronika Caisova, Garima Gupta, Katherine I Wolf, Gregg L Semenza, Zhengping Zhuang, Karel Pacak
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine tumors derived from adrenal or extra-adrenal chromaffin cells, respectively. Metastases are discovered in 3-36% of patients at the time of diagnosis. Currently, only suboptimal treatment options exist. Therefore, new therapeutic compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we investigated if anthracyclines were able to suppress the progression of metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells using in vitro and in vivo models, and demonstrated that anthracyclines, particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia response element (HRE) sites on DNA...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420826/efficacy-and-safety-of-an-orally-administered-selective-prostacyclin-receptor-agonist-selexipag-in-japanese-patients-with-pulmonary-arterial-hypertension
#4
Nobuhiro Tanabe, Satoshi Ikeda, Nobuhiro Tahara, Keiichi Fukuda, Masaru Hatano, Hiroshi Ito, Tomotaka Nakayama, Toshihisa Anzai, Akiyoshi Hashimoto, Teruo Inoue, Kouji Kajinami, Yasuki Kihara, Hideyuki Kinoshita, Koichiro Kuwahara, Toyoaki Murohara, Osamu Okazaki, Satoshi Sakai, Toru Satoh, Yutaka Takeda, Yasuchika Takeishi, Mitsugu Taniguchi, Hiroshi Watanabe, Takeshi Yamamoto, Keiko Yamauchi-Takihara, Koichiro Yoshioka, Shigetake Sasayama
BACKGROUND: Selexipag is an orally available prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. In this open-label Phase II trial, the efficacy and safety of selexipag in Japanese patients with pulmonary arterial hypertension (PAH) is examined.Methods and Results:Selexipag was administered at 200 μg twice daily and titrated up to 1,600 μg by increments of 200 μg in 37 subjects to reach the individual maximum tolerated dose. At 16 weeks, in 33 patients comprising the per-protocol set, the pulmonary vascular resistance (PVR; primary endpoint) decreased from 683...
April 18, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28417056/therapeutic-effect-of-prostaglandin-e1-in-monocrotaline-induced-pulmonary-arterial-hypertension-rats
#5
Jae Chul Lee
Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in pulmonary arterial pressure and excessive thickening and remodeling of distal small pulmonary arteries. During disease progression, PAH include increase in mean pulmonary arterial pressure, right ventricular (RV) enlargement, increased pulmonary vascular resistance, and smooth muscle hypertrophy in pulmonary arterioles. Several anti-PAH therapies targeting various pathways involved in PAH progression have been approved by the Food and Drug Adminstration...
March 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/28416983/local-conduction-during-acute-myocardial-infarction-in-rats-interplay-between-central-sympathetic-activation-and-endothelin
#6
Theofilos M Kolettis, Marianthi Kontonika, Vassilios La Rocca, Antonios P Vlahos, Giannis G Baltogiannis, Zenon S Kyriakides
We investigated the effects of autonomic dysfunction and endothelin on local conduction and arrhythmogenesis during myocardial infarction. We recorded ventricular tachyarrhythmias, monophasic action potentials, and activation sequences in wild-type and ETB-deficient rats displaying high endothelin levels. Central sympathetic inputs were examined after clonidine administration. Clonidine mitigated early and delayed arrhythmogenesis in ETB-deficient and wild-type rats, respectively. The right ventricular activation delay increased in clonidine-treated ETB-deficient rats and slightly decreased in wild-type rats...
April 2017: Journal of Arrhythmia
https://www.readbyqxmd.com/read/28416805/a-new-inhibitor-of-the-%C3%AE-arrestin-ap2-endocytic-complex-reveals-interplay-between-gpcr-internalization-and-signalling
#7
Alexandre Beautrait, Justine S Paradis, Brandon Zimmerman, Jenna Giubilaro, Ljiljana Nikolajev, Sylvain Armando, Hiroyuki Kobayashi, Lama Yamani, Yoon Namkung, Franziska M Heydenreich, Etienne Khoury, Martin Audet, Philippe P Roux, Dmitry B Veprintsev, Stéphane A Laporte, Michel Bouvier
In addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28414743/the-et-1-mediated-carbonylation-and-degradation-of-anxa1-induce-inflammatory-phenotype-and-proliferation-of-pulmonary-artery-smooth-muscle-cells-in-hps
#8
Jing He, Bin Yi, Yang Chen, Qing Huang, Huan Wang, Kaizhi Lu, Weiling Fu
Hepatopulmonary syndrome (HPS) is a serious complication of advanced liver disease, which markedly increases mortality. Pulmonary vascular remodelling (PVR) induced by circulating mediators plays an important role in the pathogenesis of HPS, while the underlying mechanism remains undefined. In the present study, we reported that endothelin-1 (ET-1) is up-regulated and annexin A1(ANXA1) is down-regulated in HPS rat, and ET-1 decreases the ANXA1 expression in a dose-dependent manner in rat pulmonary arterial smooth muscle cells (PASMCs)...
2017: PloS One
https://www.readbyqxmd.com/read/28413991/potential-role-of-endothelin-in-early-vascular-aging
#9
Michelle Trindade, Wille Oigman, Mario Fritsch Neves
Early vascular aging is a process associated with gradual alterations in the vessels, regarding to their structure and function, taking a more rapid course than normal biological aging in the arteries. In the presence of cardiovascular disease, these age-associated alterations are accelerated, contributing for the appearance or the progression of cardiovascular disease, such as high blood pressure, dyslipidemia, smoking and diabetes. Endothelin-1 (ET-1) is the most abundant and important endothelin produced by vascular cells...
April 14, 2017: Current Hypertension Reviews
https://www.readbyqxmd.com/read/28413519/amp-activated-protein-kinase-mediates-the-effects-of-lipoprotein-associated-phospholipase-a2-on-endothelial-dysfunction-in-atherosclerosis
#10
Li Yang, Hong-Liang Cong, Shu-Feng Wang, Ting Liu
The present study aimed to investigate the effects of lipoprotein-associated phospholipase A2 (Lp-PLA2) on endothelial dysfunction in an in vitro cell model of atherosclerosis, and to determine whether AMP-activated protein kinase (AMPK) mediates the effects of Lp-PLA2 on endothelial dysfunction. A total of 392 patients with coronary artery disease (CAD), including various sub-conditions, were recruited, and the plasma concentrations of Lp-PLA2 were evaluated. In addition, an in vitro model of atherosclerosis was established by exposing human umbilical vein endothelial cells (HUVECs) to oxidized low-density lipoprotein (oxLDL)...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28412541/endothelin-polymorphisms-as-a-risk-factor-for-cerebral-aneurysm-rebleeding-following-aneurysmal-subarachnoid-hemorrhage
#11
Paul M Foreman, Robert M Starke, Philipp Hendrix, Mark R Harrigan, Winfield S Fisher, Nilesh A Vyas, Robert H Lipsky, Minkuan Lin, Beverly C Walters, Jean-Francois Pittet, Mali Mathru, Christoph J Griessenauer
BACKGROUND: Aneurysm rebleeding following presentation with aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and poor functional outcome. While a substantial genetic contribution to aneurysm formation and rupture is known, the genetic influence on the risk of rebleeding is poorly understood. OBJECTIVE: To evaluate the role of common endothelin polymorphisms in aneurysm rebleeding. PATIENTS AND METHODS: Blood sample from all patients enrolled in the CARAS (Cerebral Aneurysm Renin Angiotensin System) study were used for genetic evaluation...
April 7, 2017: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28412414/endothelin-1-promotes-hypertrophic-remodelling-of-cardiac-myocytes-by-activating-sustained-signalling-and-transcription-downstream-of-endothelin-type-a-receptors
#12
Caroline R Archer, Emma L Robinson, Faye M Drawnel, H Llewelyn Roderick
G-protein coupled receptor (GPCR) mediated activation of the MAPK signalling cascade is a key pathway in the induction of hypertrophic remodelling of the heart - a response to pathological cues including hypertension and myocardial infarction. While levels of pro-hypertrophic hormone agonists of GPCRs increase during periods of greater workload to enhance cardiac output, hypertrophy does not necessarily result. Here we investigated the relationship between the duration of exposure to the pro-hypertrophic GPCR agonist endothelin-1 (ET-1) and the induction of hypertrophic remodelling in neonatal rat ventricular myocytes (NRVM) and in the adult rat heart in vivo...
April 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28409476/the-effects-of-hyperoxia-on-microvascular-endothelial-cell-proliferation-and-production-of-vaso-active-substances
#13
Ilias Attaye, Yvo M Smulders, Monique C de Waard, Heleen M Oudemans-van Straaten, Bob Smit, Michiel H Van Wijhe, Rene J Musters, Pieter Koolwijk, Angelique M E Spoelstra-de Man
BACKGROUND: Hyperoxia, an arterial oxygen pressure of more than 100 mmHg or 13% O2, frequently occurs in hospitalized patients due to administration of supplemental oxygen. Increasing evidence suggests that hyperoxia induces vasoconstriction in the systemic (micro)circulation, potentially affecting organ perfusion. This study addresses effects of hyperoxia on viability, proliferative capacity, and on pathways affecting vascular tone in cultured human microvascular endothelial cells (hMVEC)...
December 2017: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/28409408/spontaneous-recombinase-activity-of-cre-ert2-in-vivo
#14
Jasmin Kristianto, Michael G Johnson, Ryley K Zastrow, Abigail B Radcliff, Robert D Blank
Inducible Cre-ERT recombinase technology is widely used for gene targeting studies. The second generation of inducible Cre-ERT recombinase, hemizygous B6.129S-Tg(UBC-cre/ERT2)1Ejb/J (hereafter abbreviated as Cre-ERT2), a fusion of a mutated estrogen receptor and Cre recombinase, was engineered to be more efficient and specific than the original Cre-ERT. The putative mechanism of selective Cre-mediated recombination is Cre sequestration in the cytoplasm in the basal state with translocation to the nucleus only in the presence of tamoxifen...
April 13, 2017: Transgenic Research
https://www.readbyqxmd.com/read/28409007/subclinical-sleep-apnoea-and-plasma-levels-of-endothelin-1-among-young-and-healthy-adults
#15
Tobias Schoen, Stefanie Aeschbacher, Joerg D Leuppi, David Miedinger, Ursina Werthmüller, Joel Estis, John Todd, Martin Risch, Lorenz Risch, David Conen
OBJECTIVE: Obstructive sleep apnoea (OSA) is a risk factor for vascular disease and other adverse outcomes. These associations may be at least partly due to early endothelin-1 (ET-1)-mediated endothelial dysfunction (ED). Therefore, we assessed the relationships between subclinical sleep apnoea and plasma levels of ET-1. METHODS: We performed a population-based study among 1255 young and healthy adults aged 25-41 years. Cardiovascular disease, diabetes or a body mass index >35 kg/m(2) were exclusion criteria...
2017: Open Heart
https://www.readbyqxmd.com/read/28407377/biomarkers-of-microvascular-endothelial-dysfunction-predict-incident-dementia-a-population-based-prospective-study
#16
H Holm, K Nägga, E D Nilsson, F Ricci, O Melander, O Hansson, E Bachus, M Magnusson, A Fedorowski
BACKGROUND: Cerebral endothelial dysfunction occurs in a spectrum of neurodegenerative diseases. Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal endothelin-1 (CT-proET-1) and midregional pro-adrenomedullin (MR-proADM) with dementia and subtypes among community-dwelling older adults. METHODS: A population-based cohort of 5,347 individuals (men, 70%; age, 69±6 years) without prevalent dementia provided plasma for determination of MR-proANP, CT-proET-1 and MR-proADM...
April 13, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28401480/target-mediated-drug-disposition-pharmacokinetic-pharmacodynamic-model-of-bosentan-and-endothelin-1
#17
Anke-Katrin Volz, Andreas Krause, Walter Emil Haefeli, Jasper Dingemanse, Thorsten Lehr
BACKGROUND AND OBJECTIVES: Bosentan is a competitive antagonist on endothelin receptor A and B (ETA and ETB), displacing the endogenous binding partner endothelin-1 (ET-1) from its binding sites. After administration of escalating single doses of 10-750 mg as an intravenous (i.v.) infusion, bosentan showed dose-dependent pharmacokinetics (PK). The aim of this analysis was to develop a PK model of bosentan after i.v. administration including competitive antagonism with ET-1 and to analyze its influence on blood pressure and heart rate with a combined pharmacokinetic/pharmacodynamic (PK/PD) model...
April 11, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28400817/nonhuman-primate-models-of-focal-cerebral-ischemia
#18
REVIEW
Jingjing Fan, Yi Li, Xinyu Fu, Lijuan Li, Xiaoting Hao, Shasha Li
Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods...
February 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28400616/granulosa-cell-endothelin-2-expression-is-fundamental-for-ovulatory-follicle-rupture
#19
Joseph A Cacioppo, Po-Ching Patrick Lin, Patrick R Hannon, Daniel R McDougle, Arnon Gal, CheMyong Ko
Ovulation is dependent upon numerous factors mediating follicular growth, vascularization, and ultimately oocyte release via follicle rupture. Endothelin-2 (EDN2) is a potent vasoconstrictor that is transiently produced prior to follicle rupture by granulosa cells of periovulatory follicles and induces ovarian contraction. To determine the role of Edn2 expression, surgical transplant and novel conditional knockout mice were super-ovulated and analyzed. Conditional knockout mice utilized a new iCre driven by the Esr2 promoter to selectively remove Edn2...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28399019/pathophysiology-and-implications-of-intradialytic-hypertension
#20
Peter Noel Van Buren
PURPOSE OF REVIEW: Intradialytic hypertension occurs regularly in 10--15% of hemodialysis patients. A large observational study recently showed that intradialytic hypertension of any magnitude increased mortality risk comparable to the most severe degrees of intradialytic hypotension. The present review review discusses the most recent evidence underlying the pathophysiology of intradialytic hypertension and implications for its management. RECENT FINDINGS: Patients with intradialytic hypertension typically have small interdialytic weight gains, but bioimpedance spectroscopy shows these patients have significant chronic extracellular volume excess...
April 8, 2017: Current Opinion in Nephrology and Hypertension
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