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https://www.readbyqxmd.com/read/29330945/cyclosporine-a-induces-endothelin-converting-enzyme-ece-1-studies-in-vivo-and-in-vitro
#1
Samuel N Heyman, Zaid Abassi, Christian Rosenberger, Hiba Yaseen, Galia Skarjinski, Ahuva Shina, Susanne Mathia, Natalia Krits, Mogher Khamaisi
AIM: Cyclosporine A (CsA) induces renal vasoconstriction and hypoxia and enhances the expression of endothelin-1 (ET-1) pro-hormone (pre-pro ET-1), plausibly leading to a feed-forward loop of renal vasoconstriction, hypoxia, and enhanced synthesis of the potent vasoconstrictor ET-1. Endothelin converting enzyme (ECE)-1 cleaves big endothelin to generate endothelin (ET)-1 and is up-regulated by hypoxia via hypoxia-inducible factor (HIF). We hypothesized that in addition to the direct induction of ET-1 synthesis, CsA might also intensify renal ECE-1expression, thus contributing to enhanced ET-1 synthesis following CsA...
January 13, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29329779/receptor-and-cellular-compartment-specific-activation-of-the-camp-pka-pathway-by-%C3%AE-1-adrenergic-and-eta-endothelin-receptors
#2
Ryan D Martin, Yalin Sun, Kyla Bourque, Nicolas Audet, Asuka Inoue, Jason C Tanny, Terence E Hébert
The signaling functions of many G protein-coupled receptors (GPCRs) expressed in the myocardium are incompletely understood. Among these are the endothelin receptor (ETR) family and α1-adrenergic receptor (α1-AR), which are thought to couple to the G protein Gαq. In this study, we used transcriptome analysis to compare the signaling networks downstream of these receptors in primary neonatal rat cardiomyocytes. This analysis indicated increased expression of target genes of cAMP responsive element modulator (CREM) after 24 h treatment with the α1-AR agonist phenylephrine, but not the ETR agonist endothelin-1, suggesting a specific role for the α1-AR in promoting cAMP production in cardiomyocytes...
January 9, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29326427/severe-steatosis-induces-portal-hypertension-by-systemic-arterial-hyporeactivity-and-hepatic-vasoconstrictor-hyperreactivity-in-rats
#3
Denise Van der Graaff, Wilhelmus J Kwanten, Filip J Couturier, Jesse S Govaerts, Wim Verlinden, Isabel Brosius, Michiel D'Hondt, Ann Driessen, Benedicte Y De Winter, Joris G De Man, Peter P Michielsen, Sven M Francque
Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease. The presence of portal hypertension has been demonstrated in NAFLD prior to development of inflammation or fibrosis, and is a result of extrahepatic and intrahepatic factors, principally driven by vascular dysfunction. An increased intrahepatic vascular resistance potentially contributes to progression of NAFLD via intralobular hypoxia. However, the exact mechanisms underlying vascular dysfunction in NAFLD remain unknown...
January 11, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29317988/endothelin-1-activation-in-pediatric-patients-undergoing-surgical-coarctation-of-the-aorta-repair
#4
Benjamin Steven Frank, Tracy T Urban, Suhong Tong, Courtney Cassidy, Max B Mitchell, Christopher S Nichols, Jesse A Davidson
AIM: To determine endothelin-1 (ET-1) concentration before and after surgical coarctectomy and evaluate its association with left ventricular geometric change. METHODS: A prospective, cohort study of 24 patients aged 2 d to 10 years with coarctation of the aorta undergoing surgical repair. A sub-cohort of patients with age < 1 mo was classified as "neonates". Echocardiograms were performed just prior to surgery and in the immediate post-op period to assess left ventricle mass index and relative wall thickness (RWT)...
December 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/29316834/delayed-administration-of-bq788-an-etb-antagonist-after-experimental-traumatic-brain-injury-promotes-recovery-of-blood-brain-barrier-function-and-reduction-of-cerebral-edema-in-mice
#5
Shotaro Michinaga, Akimasa Kimura, Shunichi Hatanaka, Shizuho Minami, Arisa Asano, Yuki Ikushima, Shingo Matsui, Yoshiya Toriyama, Manami Fujii, Yutaka Koyama
Traumatic brain injury (TBI) is induced by immediate physical disruption of brain tissue, and causes death and disability. Studies on experimental TBI animal models show that disruption of the blood-brain barrier (BBB) underlies brain edema and neuroinflammation during the delayed phase of TBI. In neurological disorders, endothelin-1 (ET-1) is involved in BBB dysfunction and brain edema. In this study, the effect of ET antagonists on BBB dysfunction and brain edema were examined in a mouse focal TBI model using lateral fluid percussion injury (FPI)...
January 9, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29314204/telmisartan-ameliorates-vascular-endothelial-dysfunction-in-coronary-slow-flow-phenomenon-csfp
#6
Zhe Jin, Qindong Tan, Bei Sun
Coronary slow flow phenomenon (CSFP) is a coronary microvascular disorder with an increasing morbidity, and currently, available therapies are of limited clinical value for its cure. Hence, it is urgent to find a novel approach to CSFP treatment. Several studies show that endothelial dysfunction plays a critical role in the aetiology of CSFP. Telmisartan (TMST) is a clinically available anti-hypertensive medicine and has shown its potential properties for improving vascular endothelial function. Thus, we aimed to investigate the effect of TMST on endothelial dysfunction in CSFP, Endothelial-dependent flow-mediated vasodilation, serum levels of nitric oxide, adiponectin, and endothelin-1 were surveyed before and after 3 months of TMST treatment...
January 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29312703/isolated-unilateral-absence-of-pulmonary-artery-in-adulthood-a-clinical-analysis-of-65-cases-from-a-case-series-and-systematic-review
#7
Ping Wang, Ling Yuan, Juhong Shi, Zuojun Xu
Background: Isolated unilateral absence of pulmonary artery (UAPA) in adulthood is a rare congenital anomaly. Although some case reports exist, the clinical symptomatology, lung parenchymal features, collateral circulation and therapeutic approaches in adult patients with isolated UAPA remain unknown. The objectives of this study are to investigate the clinical characteristics, elucidate the correlation between clinical symptomatology and radiology, and summarize treatment of adult patients with isolated UAPA...
December 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29311252/pazopanib-induced-hypertension-in-patients-with-renal-cell-carcinoma-is-associated-with-low-urine-excretion-of-no-metabolites
#8
Anne Robdrup Tinning, Camilla Bengtsen, Niels Viggo Jensen, Lars Bastholt, Boye Lagerbon Jensen, Kirsten Madsen
Drugs targeting VEGF (vascular endothelial growth factor) are often associated with rapid development of hypertension by a yet not fully understood mechanism. VEGF is expressed in renal epithelial cells and stimulates NO production. In the renal medulla, inhibition of NO formation by local L-NAME or by impaired endothelin-1 leads to hypertension. The present study was designed to test the hypothesis that VEGF receptor inhibitor treatment leads to hypertension through decreased renal medullary formation of NO and endothelin-1...
January 8, 2018: Hypertension
https://www.readbyqxmd.com/read/29307087/targeting-the-prostacyclin-pathway-with-selexipag-in-patients-with-pulmonary-arterial-hypertension-receiving-double-combination-therapy-insights-from-the-randomized-controlled-griphon-study
#9
J Gerry Coghlan, Richard Channick, Kelly Chin, Lilla Di Scala, Nazzareno Galiè, Hossein-Ardeschir Ghofrani, Marius M Hoeper, Irene M Lang, Vallerie McLaughlin, Ralph Preiss, Lewis J Rubin, Gérald Simonneau, Olivier Sitbon, Victor F Tapson, Sean Gaine
BACKGROUND: In pulmonary arterial hypertension (PAH), combination therapy is an important treatment strategy. Although randomized controlled trial data are available to support the combination of two therapies, data regarding triple combination therapy are few. OBJECTIVE: The phase III GRIPHON trial enrolled 1156 patients with PAH, including 376 receiving background double combination therapy. We evaluated the efficacy and safety of selexipag as a third agent in these patients and further analyzed this subgroup according to symptom burden at baseline as indicated by World Health Organization (WHO) functional class (FC)...
January 6, 2018: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/29301980/mir-210-and-gpd1l-regulate-edn2-in-primary-and-immortalized-human-granulosa-lutein-cells
#10
Ketan Shrestha, Adepeju Esther Onasanya, Iris Eisenberg, Noa Wigoda, Simcha Yagel, Ronit Yalu, Rina Meidan, Tal Imbar
Endothelin-2 (EDN2), expressed at a narrow window during the periovulatory period, critically affects ovulation and corpus luteum (CL) formation. LH (acting mainly via cAMP) and hypoxia are implicated in CL formation; therefore, we aimed to elucidate how these signals regulate EDN2 using human primary (hGLCs) and immortalized (SVOG) granulosa-lutein cells. The hypoxiamiR, microRNA-210 (miR-210) was identified as a new essential player in EDN2 expression. Hypoxia (either mimetic compound-CoCl2, or low O2) elevated hypoxia inducible factor 1A (HIF1A), miR-210, and EDN2...
January 4, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29301848/physiologic-pathologic-and-therapeutic-paracrine-modulation-of-cardiac-excitation-contraction-coupling
#11
REVIEW
Joshua Mayourian, Delaine K Ceholski, David M Gonzalez, Timothy J Cashman, Susmita Sahoo, Roger J Hajjar, Kevin D Costa
Cardiac excitation-contraction coupling (ECC) is the orchestrated process of initial myocyte electrical excitation, which leads to calcium entry, intracellular trafficking, and subsequent sarcomere shortening and myofibrillar contraction. Neurohumoral β-adrenergic signaling is a well-established mediator of ECC; other signaling mechanisms, such as paracrine signaling, have also demonstrated significant impact on ECC but are less well understood. For example, resident heart endothelial cells are well-known physiological paracrine modulators of cardiac myocyte ECC mainly via NO and endothelin-1...
January 5, 2018: Circulation Research
https://www.readbyqxmd.com/read/29301417/isolated-kidney-perfusion-the-influence-of-pulsatile-flow
#12
Charlotte von Horn, Thomas Minor
Within the scope of transplantation research, ex vivo kidney perfusion has been proven an attractive model to study ischemia-reperfusion and preservation injury. Renal perfusion techniques also occupy scientists with the aim to optimize organ reconditioning and preparation prior to transplantation. This study investigated the influence of a pulsatile perfusion pattern that brings flow conditions closer to physiological situations, on renal perfusion characteristic and kidney function in the isolated perfused kidney...
January 4, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29295950/endothelin-type-b-etb-receptors-friend-or-foe-in-the-pathogenesis-of-pre-eclampsia-and-future-cardiovascular-disease-cvd-risk
#13
Katrina M Mirabito Colafella
In a recent issue of Clinical Science, Stanhewicz et al. investigated persistent microvascular dysfunction in women up to 16 months postpartum. The authors found sensitivity to the pressor effects of endothelin-1 (ET-1) was enhanced when compared with women who had a normotensive pregnancy. Importantly, the authors demonstrated that this effect was mediated via the endothelin type B (ETB) receptors. Therefore, the present study highlights the possibility that alterations in the localization of the ETB receptor contributes to the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk...
January 16, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29295858/hif-1%C3%AE-stabilization-reduces-retinal-degeneration-in-a-mouse-model-of-retinitis-pigmentosa
#14
Lorena Olivares-González, Cristina Martínez-Fernández de la Cámara, David Hervás, José María Millán, Regina Rodrigo
Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision due to rod and cone degeneration. Evidence suggests that an inappropriate oxygen level could contribute to its pathogenesis. Rod cell death could increase oxygen concentration, reduce hypoxia-inducible factor 1 (HIF-1α) and contribute to cone cell death. The purposes of this study were: 1) to analyze the temporal profile of HIF-1α, its downstream effectors VEGF, endothelin-1 (ET-1), iNOS, and glucose transporter 1 (GLUT1), and neuroinflammation in retinas of the murine model of rd10 (retinal degeneration 10) mice with RP; 2) to study oxygen bioavailability in these retinas; and 3) to investigate how stabilizing HIF-1α proteins with dimethyloxaloglycine (DMOG), a prolyl hydroxylase inhibitor, affects retinal degeneration, neuroinflammation, and antioxidant response in rd10 mice...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295855/the-%C3%AE-2-agonist-terbutaline-specifically-decreases-pulmonary-arterial-pressure-under-normoxia-and-hypoxia-via-%C3%AE-adrenoceptor-antagonism
#15
Vanessa Neumann, Ralf Knies, Alexander Seidinger, Annika Simon, Kristina Lorenz, Michaela Matthey, Johannes Breuer, Daniela Wenzel
Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β2 adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29290188/the-potential-therapeutic-role-of-peroxisome-proliferatoractivated-receptors-agonist-in-preeclamptic-pregnant-rats
#16
Hayam Ibrahim Gad Allam, Abeer AbdulMoati Al Masri
OBJECTIVE: To investigate the role of peroxisome proliferator-activated receptor (PPAR)-γ agonist on renal functions and blood levels of vasoregulatory peptides by administering rosiglitazone-a PPAR-γ agonist- to nitric oxide (NO) synthase lacking pregnant rats as a creature model of preeclampsia. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Medical College at King Khaled University Hospital, Riyadh, Saudi Arabia, from July 2016 to May 2017...
January 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/29289894/bionalytical-validation-study-for-the-determination-of-unbound-ambrisentan-in-human-plasma-using-rapid-equilibrium-dialysis-followed-by-ultra-performance-liquid-chromatography-coupled-to-mass-spectrometry
#17
Soledad Garcia-Martínez, Estitxu Rico, Enriqueta Casal, Alba Grisaleña, Eider Alcaraz, Nicholas King, Nerea Leal, Iker Navarro, Miguel Ángel Campanero
Ambrisentan is a highly selective endothelin-1 type A receptor antagonist indicated for use in the treatment of pulmonary hypertension. In this study an assay was developed and validated for the quantification of total and unbound (free) concentrations of ambrisentan in human plasma. Plasma samples were dialysed against phosphate buffered saline in a rapid equilibrium dialysis device to obtain dialysate and plasma for unbound and total ambrisentan, respectively. Subsequently, ambrisentan and deuterated ambrisentan (internal standard) were extracted from plasma or plasma dialysate by solid-phase extraction and separated by ultra performance liquid chromatography using on a reversed-phase C18 column...
December 16, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29288933/targeting-the-renin-angiotensin-system-as-novel-therapeutic-strategy-for-pulmonary-diseases
#18
REVIEW
Wan Shun Daniel Tan, Wupeng Liao, Shuo Zhou, Dan Mei, Wai-Shiu Fred Wong
The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects. Novel intervention is definitely needed to offer optimal therapeutic strategy and clinical outcome...
December 27, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29286546/serious-liver-injury-associated-with-macitentan-a-case-report
#19
Thao T Tran, Allen D Brinker, Monica Muñoz
Several endothelin receptor antagonists (ERAs) that were developed for the treatment of pulmonary arterial hypertension (PAH), including bosentan and sitaxentan, have been linked to clinically significant hepatocellular injury, as well as liver failure. We describe the first case of fulminant hepatitis to be reported in association with the ERA macitentan. This case was recently identified within the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and and describes liver transplantation occuring 13 months following macitentan initiation in a young patient (23-years old) with idiopathic PAH New York Heart Association (NYHA) functional class III...
December 29, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29286062/mir-200c-regulates-the-proliferation-apoptosis-and-invasion-of-gastric-carcinoma-cells-through-the-downregulation-of-ednra-expression
#20
Wei Wei, Li Shi, Weichang Chen, Liyu Hu, Dan Chen, Xiaoying Shi, Hua Xiang, Cunguo Guo, Zhenping Wu
This study aimed to investigate the regulatory effects of microRNA (miR)‑200c on the proliferation, apoptosis and invasion of gastric carcinoma cells and to elucidate the underlying mechanisms involving the possible role of endothelin receptor A (EDNRA). The expression levels of miR‑200c and EDNRA in the gastric carcinoma cell lines, BGC‑823, SGC‑7901 and HGC‑27, and in GES‑1 normal gastric cells were evaluated by RT‑PCR and western blot analysis. The gastric carcinoma cells, particularly the BGC‑823 cells, expressed significantly lower levels of miR‑200c than the normal gastric cells (P<0...
December 12, 2017: International Journal of Molecular Medicine
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