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Endothelin inhibitor

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https://www.readbyqxmd.com/read/28087362/clinical-phenotypes-and-outcomes-of-heritable-and-sporadic-pulmonary-veno-occlusive-disease-a-population-based-study
#1
David Montani, Barbara Girerd, Xavier Jaïs, Marilyne Levy, David Amar, Laurent Savale, Peter Dorfmüller, Andrei Seferian, Edmund M Lau, Mélanie Eyries, Jérôme Le Pavec, Florence Parent, Damien Bonnet, Florent Soubrier, Elie Fadel, Olivier Sitbon, Gérald Simonneau, Marc Humbert
BACKGROUND: Bi-allelic mutations of the EIF2AK4 gene cause heritable pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis (PVOD/PCH). We aimed to assess the effect of EIF2AK4 mutations on the clinical phenotypes and outcomes of PVOD/PCH. METHODS: We did a population-based study using clinical, functional, and haemodynamic data from the registry of the French Pulmonary Hypertension Network. We reviewed the clinical data and outcomes from all patients referred to the French Referral Centre (Pulmonary Department, Hospital Kremlin-Bicêtre, University Paris-Sud) with either confirmed or highly probable PVOD/PCH with DNA available for mutation screening (excluding patients with other risk factors of pulmonary hypertension, such as chronic respiratory diseases)...
January 10, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28060893/positioning-of-tacrolimus-for-the-treatment-of-diabetic-nephropathy-based-on-computational-network-analysis
#2
Constantin Aschauer, Paul Perco, Andreas Heinzel, Judith Sunzenauer, Rainer Oberbauer
OBJECTIVE: To evaluate tacrolimus as therapeutic option for diabetic nephropathy (DN) based on molecular profile and network-based molecular model comparisons. MATERIALS AND METHODS: We generated molecular models representing pathophysiological mechanisms of DN and tacrolimus mechanism of action (MoA) based on literature derived data and transcriptomics datasets. Shared enriched molecular pathways were identified based on both model datasets. A newly generated transcriptomics dataset studying the effect of tacrolimus on mesangial cells in vitro was added to identify mechanisms in DN pathophysiology...
2017: PloS One
https://www.readbyqxmd.com/read/28053559/systemic-lupus-erythematosus-and-pulmonary-arterial-hypertension-links-risks-and-management-strategies
#3
REVIEW
Konstantinos Tselios, Dafna D Gladman, Murray B Urowitz
Systemic lupus erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg) with normal pulmonary capillary wedge pressure (≤15 mmHg) and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram...
2017: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/28030574/endothelin-regulates-porphyromonas-gingivalis-induced-production-of-inflammatory-cytokines
#4
Ga-Yeon Son, Eun-Jung Bak, Ji-Hye Kim, Dong Eun Lee, Si-Mook Kang, So Yun Lee, Lin Choi, Ji Su Sun, Seul Ki Kim, Wonse Park, Baek Il Kim, Yun-Jung Yoo, Inik Chang, Dong Min Shin
Periodontitis is a very common oral inflammatory disease that results in the destruction of supporting connective and osseous tissues of the teeth. Although the exact etiology is still unclear, Gram-negative bacteria, especially Porphyromonas gingivalis in subgingival pockets are thought to be one of the major etiologic agents of periodontitis. Endothelin (ET) is a family of three 21-amino acid peptides, ET-1, -2, and -3, that activate G protein-coupled receptors, ETA and ETB. Endothelin is involved in the occurrence and progression of various inflammatory diseases...
2016: PloS One
https://www.readbyqxmd.com/read/28029743/statins-ameliorate-pulmonary-hypertension-secondary-to-left-ventricular-dysfunction-through-the-rho-kinase-pathway-and-nadph-oxidase
#5
I-Chen Chen, Mian-Shin Tan, Bin-Nan Wu, Chee-Yin Chai, Jwu-Lai Yeh, Shah-Hwa Chou, Ing-Jun Chen, Zen-Kong Dai
BACKGROUND: Pulmonary hypertension (PH) is a devastating disorder, for which no therapy is curative. It has been reported that pulmonary vascular remodeling, associated with increasing mean pulmonary arterial pressure and upregulated expression of endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), RhoA/RhoH-kinase results in the development of PH. Oxidative stress and the RhoA/Rho-kinase pathway are also thought to be involved in the pathophysiology of PH. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA reductase inhibitors) with pleiotropic effects and are potential agents for the treatment of PH...
December 28, 2016: Pediatric Pulmonology
https://www.readbyqxmd.com/read/28025386/tweak-up-regulates-endothelin-1-system-in-mouse-and-human-endothelial-cells
#6
Patricia Martínez-Miguel, Diana Medrano-Andrés, Mercedes Griera-Merino, Alberto Ortiz, Manuel Rodríguez-Puyol, Diego Rodríguez-Puyol, Susana López-Ongil
: TNF-like weak inducer of apoptosis (TWEAK) is a member of TNF superfamily; it has different biological functions such as inflammation, angiogenesis, proliferation and apoptosis. TWEAK and Fn14 are expressed in different cell types, including endothelial and smooth muscle cells. Despite their presence in endothelial cells, the effect of TWEAK on endothelial function is incompletely defined. AIM: To analyze the ability of TWEAK to modify the endothelin system, particularly ET-1 and ECE-1, studying the intracellular mechanisms implied...
December 25, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/28013061/voltage-and-receptor-mediated-activation-of-a-non-selective-cation-channel-in-rat-carotid-body-glomus-cells
#7
Jiaju Wang, James O Hogan, Donghee Kim
A recent study showed that hypoxia activates a Ca(2+)-sensitive, Na(+)-permeable non-selective cation channel (NSC) in carotid body glomus cells. We studied the effects of mitochondrial inhibitors that increase Ca(2+) influx via Ca(2+) channel (Cav), and receptor agonists that release Ca(2+) from endoplasmic reticulum (ER) on NSC. Mitochondrial inhibitors (NaCN, FCCP, H2S, NO) elevated [Ca(2+)]i and activated NSC. Angiotensin II and acetylcholine that elevate [Ca(2+)]i via the Gq-IP3 pathway activated NSC. However, endothelin-1 (Gq) and 5-HT (Gq) showed little or no effect on [Ca(2+)]i and did not activate NSC...
December 21, 2016: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/27997987/long-term-outcome-in-liver-transplantation-candidates-with-portopulmonary-hypertension
#8
Laurent Savale, Caroline Sattler, Audrey Coilly, Filoména Conti, Sébastien Renard, Claire Francoz, Hélène Bouvaist, Cyrille Feray, Patrick Borentain, Xavier Jaïs, David Montani, Florence Parent, Caroline O'Connell, Philippe Hervé, Marc Humbert, Gérald Simonneau, Didier Samuel, Yvon Calmus, Christophe Duvoux, François Durand, Jean Charles Duclos-Vallée, Olivier Sitbon
BACKGROUND: Portopulmonary hypertension (PoPH) is diagnosed in 2-6% of liver transplantation (LT) candidates. OBJECTIVE AND METHODS: To study outcomes of candidates for LT suffering from PoPH. Data were collected retrospectively from a prospective registry. Pulmonary hemodynamic variables were collected at the time of PoPH diagnosis, at last evaluation before LT, within 6 months and beyond 6 months after LT. RESULTS: Forty-nine patients (35 males, 48±8 years) were analysed (median MELD score 20)...
December 20, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27997891/endothelin-receptor-down-regulation-mediated-ligand-regulation-mechanisms-protect-against-cellular-hypoxia-injury-in-rat-vascular-endothelial-cells
#9
Long Li, Mushuang Hu, Long Zheng, Chao Zhang, Jiawei Li, Ruiming Rong, Tongyu Zhu, Yichen Jia
OBJECTIVE: Investigation of the effect of endothelin receptor A (ETaR)-targeting small interfering RNA (siRNA) on rat vascular endothelial cellular hypoxia injury, as well as its underlying mechanism. METHODS: An in vitro rat vascular smooth muscle cells - endothelial cells co-culture model was established and transfected with ETaR siRNA before hypoxia treatment. Cell culture supernatant, cellular protein and RNA were collected and examined at 0.5hrs, 1hrs, 2hrs, 4hrs, 8hrs, 16hrs, 24hrs and 48hrs of hypoxia with 1% oxygen...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27991911/inhibition-of-infarction-induced-sympathetic-innervation-with-endothelin-receptor-antagonism-via-a-pi3k-gsk-3%C3%AE-dependent-pathway
#10
T-M Lee, Nen-Chung Chang, Shinn-Zong Lin
Although endothelin (ET)-1 has been shown to upregulate nerve growth factor (NGF) expression, the molecular mechanisms are largely unknown. Phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase (GSK)-3β signal has been implicated in the regulation of NGF. We investigated whether selective ET receptor blockers attenuated cardiac sympathetic reinnervation through restoring PI3K/Akt/GSK-3β activity. After ligation of the left anterior descending artery, male Wistar rats were randomized to either vehicle, atrasentan (an ETA receptor antagonist) or A-192621 (an ETB receptor antagonist) for 4 weeks...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27988834/selexipag-a-review-in-pulmonary-arterial-hypertension
#11
Sean T Duggan, Susan J Keam, Celeste B Burness
Selexipag (Uptravi(®)) is an orally active, first-in-class, selective prostacyclin IP receptor agonist. Selexipag was approved recently in the EU for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO functional class (FC) II or III as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist and/or a phosphodiesterase type 5 inhibitor or as monotherapy in patients who are not candidates for these therapies, and in the USA for the treatment of PAH (WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH...
December 17, 2016: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/27982677/pathophysiological-mechanisms-of-calcineurin-inhibitor-induced-nephrotoxicity-and-arterial-hypertension
#12
L Hošková, I Málek, L Kopkan, J Kautzner
Solid organ transplantation is an established treatment modality in patients with end-stage organ damage in cases where other therapeutic options fail. The long-term outcomes of solid organ transplant recipients have improved considerably since the introduction of the first calcineurin inhibitor (CNI) - cyclosporine. In 1984, the potent immunosuppressive properties of another CNI, tacrolimus, were discovered. The immunosuppressive effects of CNIs result from the inhibition of interleukin-2 synthesis and reduced proliferation of T-cells due to calcineurin blockade...
December 16, 2016: Physiological Research
https://www.readbyqxmd.com/read/27941433/kidney-fibrosis-origins-and-interventions
#13
Thomas Vanhove, Roel Goldschmeding, Dirk Kuypers
All causes of renal allograft injury, when severe and/or sustained, can result in chronic histological damage of which interstitial fibrosis and tubular atrophy (IF/TA) are dominant features. Unless a specific disease process can be identified, what drives IF/TA progression in individual patients is often unclear. In general, clinicopathological factors known to predict and drive allograft fibrosis include graft quality, inflammation (whether 'nonspecific' or related to a specific diagnosis), infections such as polyomavirus-associated nephropathy, calcineurin inhibitors and genetic factors...
December 8, 2016: Transplantation
https://www.readbyqxmd.com/read/27932979/madagascine-induces-vasodilatation-via-activation-of-ampk
#14
Dapeng Chen, Bochao Lv, Sei Kobayashi, Yongjian Xiong, Pengyuan Sun, Yuan Lin, Salvatore Genovese, Francesco Epifano, Shanshan Hou, Fusheng Tang, Yunyan Ji, Dandan Yu
Madagascine (3-isopentenyloxyemodin) can be chemically synthesized or purified from several Rhamnus species, and it is found to have more potent biological activities than the parent compound emodin. The aim of this study is to characterize the vasodilatory effect of madagascine on vasoconstriction and sphingosylphosphorylcholine induced vasospasm in ex vivo and reveal the potential mechanisms in vitro. The effects of madagascine on vasoconstriction of rat mesenteric resistance arteries (MRAs) induced by K(+), methoxamine, and endothelin-1 were, respectively, studied...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27930693/endothelin-b-receptors-on-primary-chicken-m%C3%A3-ller-cells-and-the-human-mio-m1-m%C3%A3-ller-cell-line-activate-erk-signaling-via-transactivation-of-epidermal-growth-factor-receptors
#15
Mohammad Harun-Or-Rashid, Dardan Konjusha, Caridad Galindo-Romero, Finn Hallböök
Injury to the eye or retina triggers Müller cells, the major glia cell of the retina, to dedifferentiate and proliferate. In some species they attain retinal progenitor properties and have the capacity to generate new neurons. The epidermal growth factor receptor (EGFR) system and extracellular signal-regulated kinase (ERK) signaling are key regulators of these processes in Müller cells. The extracellular signals that modulate and control these processes are not fully understood. In this work we studied whether endothelin receptor signaling can activate EGFR and ERK signaling in Müller cells...
2016: PloS One
https://www.readbyqxmd.com/read/27910296/the-year-since-the-guidelines-a-concise-update-on-recent-advances-in-pulmonary-hypertension
#16
Abhishek Mishra, Maninder Singh, Edo Kaluski
Since the updated pulmonary hypertension (PH) guidelines published in 2015, two major landmark trials have provided additional insight regarding therapeutic algorithms of PH. In this review, we concisely summarized the key findings of peer‑reviewed studies published in the last one year in the field of PH. These studies have enhanced our therapeutic abilities by introducing a new potent agent, selexipag, and by demonstrating the advantage of upfront combination therapy (endothelin receptor antagonist and phosphodiesterase‑5 inhibitor) versus single agent therapy in group 1 PH...
February 2017: Minerva Cardioangiologica
https://www.readbyqxmd.com/read/27905989/the-histone-deacetylase-inhibitor-sodium-butyrate-exhibits-neuroprotective-effects-for-ischemic-stroke-in-middle-aged-female-rats
#17
Min Jung Park, Farida Sohrabji
BACKGROUND: Sodium butyrate (NaB) is a histone deacetylase (HDAC) inhibitor exhibiting anti-inflammatory and neuroprotective effects in a rat ischemic model of stroke as well as a myocardial ischemia model. Although clinical evidence shows that older women are at higher risk for stroke occurrence and greater stroke severity, no studies have evaluated the effectiveness of NaB either in females or in older animals. METHODS: To determine the effects of NaB on stroke in older females, acyclic middle-aged Sprague-Dawley female rats (9-11 months old, constant diestrus) were subject to middle cerebral artery occlusion (MCAo) by intracerebral injection of recombinant endothelin-1...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27905105/endothelin-1-et-1-stimulates-carboxy-terminal-smad2-phosphorylation-in-vascular-endothelial-cells-by-a-mechanism-dependent-on-et-receptors-and-de-novo-protein-synthesis
#18
Narges Sharifat, Ghorban Mohammad Zadeh, Mohammad-Ali Ghaffari, Parisa Dayati, Danielle Kamato, Peter J Little, Hossein Babaahmadi-Rezaei
OBJECTIVE: G protein-coupled receptor (GPCR) agonists through their receptors can transactivate protein tyrosine kinase receptors such as epidermal growth factor receptor and serine/threonine kinase receptors most notably transforming growth factor (TGF)-β receptor (TβRI). This signalling mechanism represents a major expansion in the cellular outcomes attributable to GPCR signalling. This study addressed the role and mechanisms involved in GPCR agonist, endothelin-1 (ET-1)-mediated transactivation of the TβRI in bovine aortic endothelial cells (BAECs)...
January 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27903663/beyond-a-single-pathway-combination-therapy-in-pulmonary-arterial-hypertension
#19
REVIEW
Olivier Sitbon, Sean Gaine
There is a strong rationale for combining therapies to simultaneously target three of the key pathways implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Evidence to support this strategy is growing, and a number of studies have demonstrated that combination therapy, administered as either a sequential or an initial regimen, can improve long-term outcomes in PAH. Dual combination therapy with a phosphodiesterase-5 inhibitor and an endothelin receptor antagonist is the most widely utilised combination regimen...
December 2016: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/27894250/pathological-interactions-between-the-endothelin-1-and-the-angiotensin-converting-enzyme-among-tunisian-coronary-patients
#20
Abdelkader Chalghoum, Yosri Noichri, Azza Dandana, Bruno Baudin, Abdelhédi Miled, Salima Ferchichi
BACKGROUND: The correct understanding of the biochemical and metabolic interactions between coronary risk factors contribute to the exploration of cardiovascular pathophysiology and improves therapeutic care. The aim of this study was to explore the endothelin-1 (ET-1) concentration and the angiotensin converting enzyme (ACE) activity among Tunisian patients with coronary heart disease, and to investigate the metabolic relationships between these two markers,… and to assess the possible relationship between them and the different risk factors...
November 29, 2016: BMC Cardiovascular Disorders
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