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Endothelin

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https://www.readbyqxmd.com/read/29451687/gpcrs-in-context-sexual-dimorphism-in-the-cardiovascular-system
#1
REVIEW
Margaret A Mouat, James L J Coleman, Nicola J Smith
Cardiovascular disease remains the largest cause of mortality worldwide and there is a clear gender gap in disease occurrence: men are predisposed to earlier onset of cardiovascular disease, including atherosclerosis and hypertension, than are women. Oestrogen may be a driving factor for female-specific cardioprotection, though androgens and sex chromosomes are also likely to contribute to sexual dimorphism in the cardiovascular system. Many G protein-coupled receptor (GPCR)-mediated processes are involved in cardiovascular homeostasis and some exhibit clear sex-divergence...
February 16, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29449619/chronic-et-a-antagonist-reverses-hypertension-and-impairment-of-structure-and-function-of-peripheral-small-arteries-in-aortic-stiffening
#2
Xiaomei Guo, Huan Chen, Ling Han, Stephan Haulon, Ghassan S Kassab
Arterial stiffness may contribute to the pathogenesis of hypertension. The goal of this study is to elucidate the role of Endothelin-1 (ET-1) in aortic stiffening-induced hypertension through ET A receptor activation. An increase in aortic stiffness was created by use of a non-constrictive restraint, NCR on the abdominal aortic surface. A group of rats underwent aortic NCR or sham operation for 12 weeks and were then treated with ET A receptor antagonist BQ-123 for 3 weeks. We found that 12 weeks of aortic NCR significantly increased pulse and mean pressure and altered peripheral flow pattern, accompanied by an increased serum ET-1 level (p < 0...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29448283/-significance-of-endothelin-1-in-glaucoma-a-short-overview
#3
Konstantin Gugleta
This review article is focused on the various facets of possible endothelin's role in glaucoma; involvement of endothelin in other ocular, in particular vascular, diseases is not specifically discussed. Endothelin is an ubiquitous molecule that occurs in practically all ocular tissues. Its primary physiological function is regulation of the blood vessel diameter and hence regulation of the blood supply in tissues. It is secreted locally, and exerts its effect also predominantly locally. This limits the value of venous blood sampling for estimation of the endothelin function in a particular patient, or in study cohorts as well...
February 2018: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/29448245/a-genetic-variant-associated-with-the-five-vascular-diseases-is-a-distal-regulator-of-endothelin-1-gene-expression
#4
Ernesto L Schiffrin
Gupta et al. [Cell 2017; 170: 522-533] have shown that a genetic variant associated with the 5 vascular diseases is a distal regulator of endothelin (ET)-1 gene (EDN1) expression. A common single nucleotide polymorphism (SNP) in the third intron of the PHACTR1 gene, rs9349379, is the potential variant responsible for increased risk of coronary artery disease, and lower risk of migraine, carotid dissection, fibromuscular dysplasia, and hypertension. Since ET-1 acts through ET type B receptors (ETBR) on endothelial cells to stimulate the production of nitric oxide and prostacyclin and induce vasodilation, this may contribute to these findings...
February 15, 2018: Nephron
https://www.readbyqxmd.com/read/29446710/early-versus-late-cardiac-remodelling-during-right-ventricular-pressure-load-and-impact-of-preventive-versus-rescue-therapy-with-endothelin-1-receptor-blockers
#5
Sara Roldan Ramons, Guido Ehrenfried Pieles, Mei Sun, Cameron Slorach, Wei Hui, Mark K Friedberg
BACKGROUND: Pulmonary artery banding (PAB) causes right ventricular (RV) dysfunction, biventricular fibrosis and apoptosis which are attenuated by endothelin-1 (ET1) receptor blockade (ERB). Little is known about the time-course of remodelling and whether early versus late ERB confers improved outcome. MATERIALS AND METHODS: PAB was performed in 5-groups of rabbits: Shams, 3W (3-weeksPAB), 6W (6-weeksPAB), 6WERB1 (6-weeksPAB+ERB from day-1) and 6WERB21 (6-weeksPAB+ERB from day-21)...
February 15, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29444773/lung-function-inflammation-and-endothelin-1-in-congenital-heart-disease-associated-pulmonary-arterial-hypertension
#6
Andrew Low, Sarah George, Luke Howard, Nicholas Bell, Ann Millar, Robert M R Tulloh
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...
February 14, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29440474/neuroprotective-effects-of-magl-monoacylglycerol-lipase-inhibitors-in-experimental-ischemic-stroke
#7
Sang-Ho Choi, Allison L Arai, Yongshan Mou, Byeongteck Kang, Cecil Chern-Chyi Yen, John Hallenbeck, Afonso C Silva
BACKGROUND AND PURPOSE: MAGL (monoacylglycerol lipase) is an enzyme that hydrolyzes the endocannabinoid 2-arachidonoylglycerol and regulates the production of arachidonic acid and prostaglandins-substances that mediate tissue inflammatory response. Here, we have studied the effects of the selective MAGL inhibitors JZL184 and MJN110 and their underlying molecular mechanisms on 3 different experimental models of focal cerebral ischemia. METHODS: SHR (spontaneously hypertensive rats) and normotensive WKY (Wistar Kyoto) rats were subject to an intracortical injection of the potent vasoconstrictor endothelin-1, permanent occlusion of a distal segment of the middle cerebral artery via craniectomy, or transient occlusion of the middle cerebral artery by the intraluminal suture method...
February 13, 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29439204/hmena-is-a-key-regulator-in-endothelin-1-%C3%AE-arrestin1-induced-invadopodial-function-and-metastatic-process
#8
Francesca Di Modugno, Valentina Caprara, Lidia Chellini, Piera Tocci, Francesca Spadaro, Gabriella Ferrandina, Andrea Sacconi, Giovanni Blandino, Paola Nisticò, Anna Bagnato, Laura Rosanò
Aberrant activation of endothelin-1 receptors (ET-1R) elicits pleiotropic effects relevant for tumor progression. The network activated by this receptor might be finely, spatially, and temporarily orchestrated by β-arrestin1 (β-arr1)-driven interactome. Here, we identify hMENA, a member of the actin-regulatory protein ENA/VASP family, as an interacting partner of β-arr1, necessary for invadopodial function downstream of ET-1R in serous ovarian cancer (SOC) progression. ET-1R activation by ET-1 up-regulates expression of hMENA/hMENAΔv6 isoforms through β-arr1, restricted to mesenchymal-like invasive SOC cells...
February 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29438081/microvasospasms-after-experimental-subarachnoid-hemorrhage-do-not-depend-on-endothelin-a-receptors
#9
Hanhan Liu, Ari Dienel, Karsten Schöller, Susanne M Schwarzmaier, Kathrin Nehrkorn, Nikolaus Plesnila, Nicole A Terpolilli
BACKGROUND AND PURPOSE: Perturbations in cerebral microcirculation (eg, microvasospasms) and reduced neurovascular communication determine outcome after subarachnoid hemorrhage (SAH). ET-1 (endothelin-1) and its receptors have been implicated in the pathophysiology of large artery spasms after SAH; however, their role in the development of microvascular dysfunction is currently unknown. Here, we investigated whether inhibiting ET A (endothelin A) receptors can reduce microvasospasms after experimentally induced SAH...
February 8, 2018: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29436260/treatment-patterns-and-associated-health-care-costs-before-and-after-treatment-initiation-among-pulmonary-arterial-hypertension-patients-in-the-united-states
#10
Charles D Burger, A Burak Ozbay, Howard M Lazarus, Ellen Riehle, Leslie B Montejano, Gregory Lenhart, R James White
BACKGROUND: Despite multiple treatment options, the prognosis of pulmonary arterial hypertension (PAH) remains poor. PAH patients experience a high economic burden due to comorbidities, hospitalizations, and medication costs. Although combination therapy has been shown to reduce hospitalizations, the relationship between treatment, health care utilization, and costs remains unclear. OBJECTIVE: To provide a characterization of health care utilization and costs in real-world settings by comparing periods before and after initiating PAH-specific treatment...
February 13, 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29434789/effects-of-pumpless-extracorporeal-lung-assist-on-hemodynamics-gas-exchange-and-inflammatory-cascade-response-during-experimental-lung-injury
#11
Zhihai Ju, Jinhui Ma, Chen Wang, Jie Yu, Yeru Qiao, Feilong Hei
Pumpless extracorporeal lung assist (pECLA) has been reported to efficiently remove the systemic CO 2 production and provide mild to moderate oxygenation, thereby allowing for ventilator settings and modes prioritizing oxygenation and lung protection. However, an adequate bypass flow, the capacity to provide respiratory support and the effect on the inflammatory cascade response and tissue perfusion require further study to be determined. After induction of acute lung injury (ALI) by oleic acid injection, pECLA was implemented in 12 anaesthetized and mechanically ventilated dogs for 48 h...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434725/a-novel-hypothermic-machine-perfusion-system-using-a-lifeport-kidney-transporter-for-the-preservation-of-rat-liver
#12
Cheng Zeng, Xiaoyan Hu, Yanfeng Wang, Xianpeng Zeng, Yan Xiong, Ling Li, Qifa Ye
The protective mechanisms for liver preservation associated with hypothermic machine perfusion (HMP) remain unclear. However, the lack of a common and portable HMP system for rat livers limits the study of HMP. The present study aimed to develop a novel, modified HMP system using a LifePort Kidney Transporter for preserving rat livers. A simple 'Y' shunt combined with a pressoreceptor for flow and pressure regulation was adapted to perfuse rat livers via the portal vein continuously using a LifePort Kidney Transporter under its 'prime mode' setting...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29432709/neprilysin-inhibition-and-endothelin-1-elevation-focus-on-the-kidney
#13
Lodi C W Roksnoer, Estrellita Uijl, René de Vries, Ingrid M Garrelds, A H Jan Danser
Increasing the degree of renin-angiotensin system (RAS) blockade by combining ≥2 RAS blockers marginally increases efficacy, but results in more side effects. Hence, interference with other systems is currently being investigated, like potentiation of natriuretic peptides with neprilysin inhibitors. However, the neprilysin inhibitor thiorphan was recently found to increase endothelin-1 when administered to TGR(mREN2)27 (Ren2) rats on top of RAS blockade. Here we investigated whether this effect is thiorphan-specific, by comparing the neprilysin inhibitors thiorphan and sacubitril, administered by osmotic minipumps at a low or high dose for 7 days, in Ren2 rats...
February 9, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29432661/is-pulmonary-vascular-disease-reversible-with-ppar-%C3%A9-agonists
#14
Peter Afdal, Antoine F AbdelMassih
Severe angio-obliterative pulmonary vascular disease (PAH) remains a disease characterized by great morbidity and shortened survival. Unfortunately, the only currently available treatments for angio-obliterative changes are palliative in the form of pulmonary vasodilators evolving from the phosphodiesterase inhibitor sildenafil to endothelin receptor antagonist: Bosentan; while the only definitive treatment is lung transplantation which remains dependent on the availability of donors and the transplant policies which vary widely from a country to another...
February 12, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/29431284/increased-blood-lactate-is-prevalent-and-identifies-poor-prognosis-in-patients-with-acute-heart-failure-without-overt-peripheral-hypoperfusion
#15
Robert Zymliński, Jan Biegus, Mateusz Sokolski, Paweł Siwołowski, Sylwia Nawrocka-Millward, John Todd, Ewa A Jankowska, Waldemar Banasiak, Gad Cotter, John G Cleland, Piotr Ponikowski
AIMS: Lactate is produced by anaerobic metabolism and may reflect inadequate tissue perfusion in conditions such as acute heart failure (AHF). We evaluated the prevalence and clinical significance of elevated blood lactate on admission in patients with AHF. METHODS AND RESULTS: We enrolled 237 patients with AHF (mean age 67 ± 12 years; 70% men) presenting without overt clinical evidence of peripheral hypoperfusion ('warm haemodynamic profile'). Median (upper and lower quartiles) blood lactate on admission was 1...
February 12, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29427643/new-mechanism-underlying-il-31-induced-atopic-dermatitis
#16
Jianghui Meng, Masaki Moriyama, Micha Feld, Joerg Buddenkotte, Timo Buhl, Attila Szöllösi, Jingming Zhang, Paul Miller, Andre Ghetti, Michael Fischer, Peter W Reeh, Chunxu Shan, Jiafu Wang, Martin Steinhoff
BACKGROUND: T helper type 2 cell-released interleukin 31 (IL-31) is a critical mediator in atopic dermatitis (AD), a prevalent and debilitating chronic skin disorder. Brain-derived natriuretic peptide (BNP) has been described as a central itch mediator. The importance of BNP in peripheral (skin-derived) itch and its functional link to IL-31 within the neuro-immune axis of the skin is unknown. OBJECTIVE: To investigate the function of BNP in the peripheral sensory system and skin in IL-31-induced itch and neuro-epidermal communication in AD...
February 7, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29416916/genotyping-and-mrna-profiling-reveal-actionable-molecular-targets-in-biliary-tract-cancers
#17
Kyriaki Papadopoulou, Samuel Murray, Kyriaki Manousou, Ioannis Tikas, Christos Dervenis, Joseph Sgouros, Dimitra Rontogianni, Sotirios Lakis, Mattheos Bobos, Christos Poulios, Stavroula Pervana, Georgios Lazaridis, George Fountzilas, Vassiliki Kotoula
Biliary tract cancer (BTC) represents a heterogeneous disease with dismal outcome. Herein, we examined genotype and angiogenesis features in BTC. We applied genotyping (Sanger, qPCR, 101-gene panel NGS), mRNA relative quantification methods, and β-catenin immunohistochemistry in 84 FFPE BTC (55 gallbladder [GBC], 14 intrahepatic [ICC], 15 extrahepatic [ECC] carcinomas). We identified 541 mutations in 68 (81%) tumors. Top mutated genes were CTNNB1 (36%); PTEN (33%); TP53 (31%); PIK3R1 (29%); PIK3CA (13%); BRCA2 and KRAS (12%); BRCA1 (11%)...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29413495/effects-of-respiratory-muscle-training-on-endothelium-and-oxidative-stress-biomarkers-in-hemodialysis-patients-a-randomized-clinical-trial
#18
Nataly Gurgel Campos, Débora Fortes Marizeiro, Ana Carolina Lins Florêncio, Ítalo Caldas Silva, Gdayllon Cavalcante Meneses, Gabriela Freire Bezerra, Alice Maria Costa Martins, Alexandre Braga Libório
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...
January 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29412765/nomad-biosensors-a-new-multiplexed-technology-for-the-screening-of-gpcr-ligands
#19
Rosa M Mella, Danel Kortazar, Meritxell Roura-Ferrer, Clarisa Salado, María Valcárcel, Amaia Castilla, Patricia Villacé
Nomad Technology (Innoprot [Innovative Technologies in Biological Systems], Derio, Spain), a novel tool for multiplexing high-throughput cell-based G protein-coupled receptor (GPCR) assays, is described in this work. This new technology comprises a family of fluorescent biosensors called Nomad Biosensors that allow for the measurement of responses mediated by G proteins through their interactions with second-messenger transduction proteins. GPCRs are one of the largest protein families of receptors in eukaryotes, and their signaling mediates important physiological processes within cells...
February 1, 2018: SLAS Technology
https://www.readbyqxmd.com/read/29412230/protective-effect-of-dexmedetomidine-against-myocardial-ischemia-reperfusion-injury-in-rabbits
#20
Jianjun Ren, Changfa Li, Yan Liu, Haitao Liu, Zhenming Dong
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)...
January 2018: Acta Cirúrgica Brasileira
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