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Endothelin inhibitor

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https://www.readbyqxmd.com/read/28214885/signaling-pathway-for-endothelin-1-and-phenylephrine-induced-camp-response-element-binding-protein-activation-in-rat-ventricular-myocytes-role-of-inositol-1-4-5-trisphosphate-receptors-and-camkii
#1
Krishna P Subedi, Min-Jeong Son, Bojjibabu Chidipi, Seong-Woo Kim, Jun Wang, Kyeong-Hee Kim, Sun-Hee Woo, Joon-Chul Kim
BACKGROUND/AIMS: Endothelin-1 (ET-1) and the α<Sub>1</Sub>-adrenoceptor agonist phenylephrine (PE) activate cAMP response element binding protein (CREB), a transcription factor implicated in cardiac hypertrophy. The signaling pathway involved in CREB activation by these hypertrophic stimuli is poorly understood. We examined signaling pathways for ET-1- or PE-induced cardiac CREB activation. METHODS: Western blotting was performed with pharmacological and genetic interventions in rat ventricular myocytes...
January 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28195067/the-effect-of-short-term-treatment-with-probiotic-vsl-3-on-various-clinical-and-biochemical-parameters-in-patients-with-liver-cirrhosis
#2
W Marlicz, E Wunsch, M Mydlowska, M Milkiewicz, K Serwin, M Mularczyk, P Milkiewicz, J Raszeja-Wyszomirska
The evidence is mounting that alterations of innate immunity and gut microbiota contribute to chronic liver disease and its complications. Modulation of intestinal microbiota is an emerging therapeutic strategy in hepatology. Probiotics through modulation of intestinal milieu have the potential to affect the course of liver disease. The data concerning the influence of probiotics on various plasma molecules and compounds involved in the pathogenesis of hyperdynamic circulatory state in liver cirrhosis is still not confluent and require further evaluation...
December 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28190786/survival-in-portopulmonary-hypertension-outcomes-of-the-united-kingdom-national-pulmonary-arterial-hypertension-registry
#3
Sasiharan Sithamparanathan, Arun Nair, Logan Thirugnanasothy, J Gerry Coghlan, Robin Condliffe, Konstantinos Dimopoulos, Charlie A Elliot, Andrew J Fisher, Sean Gaine, J Simon R Gibbs, Michael A Gatzoulis, Clive E Handler, Luke S Howard, Martin Johnson, David G Kiely, James L Lordan, Andrew J Peacock, Joanna Pepke-Zaba, Benjamin E Schreiber, Karen K K Sheares, Stephen J Wort, Paul A Corris
BACKGROUND: Portopulmonary hypertension (PoPH) is a rare condition associated with poor survival, and the effect of modern therapies that target pulmonary arterial hypertension (PAH) on long-term outcome is unknown. This study investigated the baseline characteristics and survival in the cohort of patients diagnosed with PoPH in the United Kingdom National Pulmonary Hypertension Service. METHODS: A retrospective review was conducted of all incident treatment-naïve patients with PoPH within the United Kingdom national registry diagnosed between January 2001 and December 2010...
December 31, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28183818/normalization-of-hemoglobin-based-oxygen-carrier-201-induced-vasoconstriction-roles-of-nitric-oxide-scavenging-and-endothelin
#4
Yannick J Taverne, Daphne P M de Wijs-Meijler, Maaike Te Lintel Hekkert, Paula F Moon-Massat, Greg P Dubé, Dirk Jan Duncker, Daphne Merkus
BACKGROUND: Hemoglobin-based oxygen carrier (HBOC)-201 is a cell-free modified hemoglobin solution potentially facilitating oxygen uptake and delivery in cardiovascular disorders and hemorrhagic shock. Clinical use has been hampered by vasoconstriction in the systemic and pulmonary beds. Therefore we aimed to 1) determine the possibility of counteracting HBOC-201-induced pressor effects with adenosine (ADO), 2) assess the potential roles of nitric oxide (NO) scavenging, reactive oxygen species (ROS) and endothelin (ET) in mediating the observed vasoconstriction and 3) compare these effects in resting and exercising swine...
February 9, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28178968/imatinib-relaxes-the-pulmonary-venous-bed-of-guinea-pigs
#5
Nina A Maihöfer, Said Suleiman, Daniela Dreymüller, Paul W Manley, Rolf Rossaint, Stefan Uhlig, Christian Martin, Annette D Rieg
BACKGROUND: Recently, the IMPRES study revealed that systemic imatinib improves exercise capacity in patients with advanced pulmonary arterial hypertension. Imatinib blocks the tyrosine kinase activity of the platelet-derived growth factor (PDGF)-receptor (PDGFR), acts antiproliferative and relaxes pulmonary arteries. However so far, the relaxant effects of imatinib on pulmonary veins (PVs) and on the postcapillary resistance are unknown, although pulmonary hypertension (PH) due to left heart disease (LHD) is most common and primarily affects PVs...
February 8, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28155615/the-protective-effect-of-dl0805-derivatives-on-pulmonary-artery-cells-and-the-underlying-mechanisms-study
#6
Tianyi Yuan, Huifang Zhang, Yucai Chen, Xiaozhen Jiao, Ping Xie, Lianhua Fang, Guanhua Du
Pulmonary hypertension (PH) is a severe disease characterized by a progressive increase in pulmonary vascular resistance, initially due to abnormal pulmonary vasoconstriction in response to endothelial and smooth muscle cells injury. The discovery of new chemical entities having a protective effect on pulmonary artery cells could be meaningful for the treatment of PH. We evaluated the protective effect of DL0805 derivatives (DL0805-1 and DL0805-2) on pulmonary artery vascular cells, including human pulmonary artery endothelial cells (HPAECs) and human pulmonary artery smooth muscle cells (HPASMCs)...
February 1, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28153500/endothelin-causes-transactivation-of-the-egfr-and-her2-in-non-small-cell-lung-cancer-cells
#7
Terry W Moody, Irene Ramos-Alvarez, Paula Moreno, Samuel A Mantey, Lisa Ridnour, David Wink, Robert T Jensen
Endothelin (ET)-1 is an important peptide in cancer progression stimulating cellular proliferation, tumor angiogenesis and metastasis. ET-1 binds with high affinity to the ETA receptor (R) and ETBR on cancer cells. High levels of tumor ET-1 and ETAR are associated with poor survival of lung cancer patients. Here the effects of ET-1 on epidermal growth factor (EGF)R and HER2 transactivation were investigated using non-small cell lung cancer (NSCLC) cells. ETAR mRNA was present in all 10 NSCLC cell lines examined...
January 31, 2017: Peptides
https://www.readbyqxmd.com/read/28152298/salubrinal-alleviates-pressure-overload-induced-cardiac-hypertrophy-by-inhibiting-endoplasmic-reticulum-stress-pathway
#8
Shilpa Rani, Pradeep Kumar Sreenivasaiah, Chunghee Cho, Do Han Kim
Pathological hypertrophy of the heart is closely associated with endoplasmic reticulum stress (ERS), leading to maladaptations such as myocardial fibrosis, induction of apoptosis, and cardiac dysfunctions. Salubrinal is a known selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phospho-eukaryotic translation initiation factor 2 subunit (p-eIF2)-α, the key signaling process in the ERS pathway. In this study, the effects of salubrinal were examined on cardiac hypertrophy using the mouse model of transverse aortic constriction (TAC) and cell model of neonatal rat ventricular myocytes (NRVMs)...
January 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28139522/ovarian-fibrosis-a-phenomenon-of-concern
#9
REVIEW
Feng Zhou, Li-Bing Shi, Song-Ying Zhang
OBJECTIVE: Ovarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis. DATA SOURCES: We searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-γ), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28133468/changing-the-treatment-of-heart-failure-with-reduced-ejection-fraction-clinical-use-of-sacubitril-valsartan-combination
#10
REVIEW
Edgardo Kaplinsky
Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitril valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the first in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II)...
November 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28120456/endothelin-1-mediates-natriuresis-but-not-polyuria-during-vitamin-d-induced-acute-hypercalcemia
#11
Natsuko Tokonami, Lydie Cheval, Isabelle Monnay, Guillaume Meurice, Johaness Loffing, Eric Feraille, Pascal Houillier
Acute hypercalcemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. As vitamin D-induced hypercalcemia increases the renal expression of endothelin (ET)-1, we hypothesized that ET-1 mediates the effects of hypercalcemia on renal sodium and water handling. Hypercalcemia was induced in 8 week-old, PTH-supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT-treated mice became hypercalcemic and displayed increased urinary water and sodium excretion compared to controls...
January 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28115513/proton-pump-inhibitors-decrease-soluble-fms-like-tyrosine-kinase-1-and-soluble-endoglin-secretion-decrease-hypertension-and-rescue-endothelial-dysfunction
#12
Kenji Onda, Stephen Tong, Sally Beard, Natalie Binder, Masanaga Muto, Sevvandi N Senadheera, Laura Parry, Mark Dilworth, Lewis Renshall, Fiona Brownfoot, Roxanne Hastie, Laura Tuohey, Kirsten Palmer, Toshihiko Hirano, Masahito Ikawa, Tu'uhevaha Kaitu'u-Lino, Natalie J Hannan
Preeclampsia is a severe complication of pregnancy. Antiangiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin are secreted in excess from the placenta, causing hypertension, endothelial dysfunction, and multiorgan injury. Oxidative stress and vascular inflammation exacerbate the endothelial injury. A drug that can block these pathophysiological steps would be an attractive treatment option. Proton pump inhibitors (PPIs) are safe in pregnancy where they are prescribed for gastric reflux...
March 2017: Hypertension
https://www.readbyqxmd.com/read/28087362/clinical-phenotypes-and-outcomes-of-heritable-and-sporadic-pulmonary-veno-occlusive-disease-a-population-based-study
#13
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)...
February 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28060893/positioning-of-tacrolimus-for-the-treatment-of-diabetic-nephropathy-based-on-computational-network-analysis
#14
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
#15
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
#16
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
#17
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
#18
Patricia Martínez-Miguel, Diana Medrano-Andrés, Mercedes Griera-Merino, Alberto Ortiz, Manuel Rodríguez-Puyol, Diego Rodríguez-Puyol, Susana López-Ongil
AIM: To analyse the ability of TWEAK to modify the endothelin system, particularly endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1), studying the intracellular mechanisms implied. 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 fibroblast growth-factor-inducible 14 are expressed in different cell types, including endothelial and smooth muscle cells...
February 2017: 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
#19
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...
March 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/27997987/long-term-outcome-in-liver-transplantation-candidates-with-portopulmonary-hypertension
#20
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
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