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Endothelin inhibitor

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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
#1
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
#2
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
#3
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
#4
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/29295858/hif-1%C3%AE-stabilization-reduces-retinal-degeneration-in-a-mouse-model-of-retinitis-pigmentosa
#5
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/29280064/macitentan-in-pulmonary-arterial-hypertension-a-focus-on-combination-therapy-in-the-seraphin-trial
#6
REVIEW
Pavel Jansa, Tomás Pulido
SERAPHIN was a double-blind, placebo-controlled, event-driven phase III trial that evaluated the effects of long-term treatment with macitentan, an oral endothelin receptor antagonist, in patients with pulmonary arterial hypertension (PAH). The majority of patients were receiving PAH therapy at enrollment, providing the opportunity to evaluate the efficacy and safety of macitentan in combination with other PAH therapies (predominantly phosphodiesterase type 5 inhibitors [PDE-5i]). In patients receiving background therapy, macitentan reduced the risk of morbidity/mortality by 38% compared with placebo (hazard ratio [HR] 0...
December 26, 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/29251627/pbx-transcription-factors-drive-pulmonary-vascular-adaptation-to-birth
#7
David J McCulley, Mark D Wienhold, Elizabeth A Hines, Timothy A Hacker, Allison Rogers, Ryan J Pewowaruk, Rediet Zewdu, Naomi C Chesler, Licia Selleri, Xin Sun
A critical event in the adaptation to extrauterine life is relaxation of the pulmonary vasculature at birth, allowing for a rapid increase in pulmonary blood flow that is essential for efficient gas exchange. Failure of this transition leads to pulmonary hypertension (PH), a major cause of newborn mortality associated with preterm birth, infection, hypoxia, and malformations including congenital diaphragmatic hernia (CDH). While individual vasoconstrictor and dilator genes have been identified, the coordination of their expression is not well understood...
December 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29233198/clinical-efficacy-and-safety-of-switch-from-bosentan-to-macitentan-in-children-and-young-adults-with-pulmonary-arterial-hypertension
#8
Ebru Aypar, Dursun Alehan, Tevfik Karagöz, Hayrettin Hakan Aykan, İlker Ertugrul
BACKGROUND: Macitentan is an orally active, potent, dual endothelin receptor antagonist and is the only registered treatment for pulmonary arterial hypertension that significantly reduced morbidity and mortality in a long-term event-driven study. Aim Few studies compared the clinical efficacy and safety of switch from bosentan to macitentan only in adult patients with pulmonary arterial hypertension. We aimed to evaluate the clinical efficacy and safety of switch from bosentan to macitentan in children and young adults...
December 13, 2017: Cardiology in the Young
https://www.readbyqxmd.com/read/29222290/chronic-organ-failure-in-adult-sickle-cell-disease
#9
REVIEW
Elliott Vichinsky
Sickle cell disease is now a chronic adult illness characterized by progressive multiorgan failure, particularly involving the brain and kidney. The etiology is multifactorial; it includes hemolysis and nitric oxide deficiency. As patients age, most experience neurologic insult. Twenty-five percent of older adults have had a clinical stroke and at least half of the population have had a silent infarct, cortical atrophy, and neurocognitive impairment. Periodic screening with neuroimaging and neurocognitive testing is recommended...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29216624/sildenafil-viagra%C3%A2-prevents-cox-1-txa2-pathway-mediated-vascular-hypercontractility-in-apoe-mice
#10
Marcos A S Leal, Ananda T Dias, Marcella L Porto, Bruna F Brun, Agata L Gava, Silvana S Meyrelles, José Gil-Longo, Manuel Campos-Toimil, Thiago M C Pereira, Elisardo C Vasquez
BACKGROUND/AIMS: The atherosclerotic apolipoprotein E-deficient (apoE-/-) mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a) to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2), thromboxane A2 (TXA2) and endothelin-1 (ET-1) to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b) to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction...
December 7, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29212810/heme-oxygenase-1-is-a-potent-inhibitor-of-placental-ischemia-mediated-endothelin-1-production-in-cultured-human-glomerular-endothelial-cells
#11
Bhavisha A Bakrania, Frank T Spradley, Simon C Satchell, David E Stec, John M Rimoldi, Rama S V Gadepalli, Joey P Granger
Preeclampsia is a pregnancy-specific disorder of maternal hypertension and reduced renal hemodynamics linked to reduced endothelial function. Placental ischemia is thought to be the culprit of this disease, as it causes the release of factors like tumor necrosis factor (TNF)-α that induce vascular endothelin-1 (ET-1) production. Interestingly, placental ischemia-induced hypertension in rats (reduced uterine perfusion pressure, RUPP model) is abolished by ETA receptor blockade, suggesting a critical role for ET-1...
December 6, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29212172/safflor-yellow-b-reduces-hypoxia-mediated-vasoconstriction-by-regulating-endothelial-micro-ribonucleic-acid-nitric-oxide-synthase-signaling
#12
Chaoyun Wang, Ying Yang, Miao Li, Xin Liu, Qiaoyun Wang, Wenyu Xin, Hongliu Sun, Qingyin Zheng
Hypoxia-induced generation of vasoconstrictors reduces cerebral blood flow (CBF) while nitric oxide (NO) synthase (NOS) and microRNAs (miRNA) in endothelial cells (ECs) suppress vasoconstriction. Safflor yellow B (SYB), a natural plant compound, previously attenuated angiotensin II-mediated injury of ECs and maintained endothelial function. This study investigated the putative involvement of NOS and miRNAs in SYB-mediated resistance to hypoxia-induced vasoconstriction. In vivo, chronic hypoxia was induced in rats, and SYB was administered intravenously...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29210632/role-of-matrix-metalloproteinases-in-degenerative-kidney-disorders
#13
Shifa Narula, Chanderdeep Tandon, Simran Tandon
Matrix metalloproteinases (MMPs) are members of calcium dependent-zinc containing endopeptidases that play a pivotal role in extracellular matrix (ECM) remodeling. MMPs are also known to cleave non-matrix proteins, including cell surface receptors, TNF-α, angiotensin-II, growth factors, (especially transforming growth factor-β1, ΤGF-β1) plasminogen, endothelin and other bioactive molecules. The tissue inhibitors of metalloproteinases (TIMPs) inhibit the activity of MMPs and decrease ECM degradation. Various patho-physiological conditions have been linked with the imbalance of ECM synthesis and degradation...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29201228/insect-tea-attenuates-hydrochloric-acid-and-ethanol-induced-mice-acute-gastric-injury
#14
Xin Zhao, Qiang Cheng, Yu Qian, Ruokun Yi, Lianjie Gu, Shanshan Wang, Jia-Le Song
The aim of the present study was to investigate the protective effect of insect tea on HCl/ethanol-induced gastric ulcers in ICR mice. The serum levels of vasoactive intestinal peptide, substance P, somatostatin, motilin and endothelin-1 in mice were assessed using commercial kits and gastric tissues of superoxide dismutase (SOD, nitric oxide (NO) and malondialdehyde (MDA) were determined using western blot analysis Insect tea significantly reduced HCl/ethanol-induced gastric juice secretion and increased the pH of gastric juice (P<0...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29185789/integrated-treatment-of-prostaglandin-e1-and-angiotensin-converting-enzyme-inhibitor-in-diabetic-kidney-disease-rats-possible-role-of-antiapoptosis-in-renal-tubular-epithelial-cells
#15
Yaru Mou, Yaqin Zhang, Congcong Guo, Junyu Zhao, Zhongwen Zhang, Xiaojun Zhou, Jianjun Dong, Lin Liao
To investigate the therapeutic mechanisms underlying prostaglandin E1 (PGE1) and angiotensin-converting enzyme inhibitor (ACEI) on reducing urinary protein in diabetic kidney disease (DKD). DKD rats were established and randomly divided into four groups: PGE1 (10 μg/kg/day) (P group), ACEI (10 mg/kg/day) (A group), combination of PGE1 with ACEI treatment (P + A group), and saline treatment group (DKD group). Untreated rats were used as normal control (N group). Urinary albumin, endothelin-1 (ET-1), angiotensin II (AngII), TUNEL assay, Masson's trichrome staining, and immunohistochemistry staining for CD68 were evaluated in all groups...
November 29, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/29165873/andrographolide-inhibits-hypoxia-induced-hypoxia-inducible-factor-1%C3%AE-and-endothelin-1-expression-through-the-heme-oxygenase-1-co-cgmp-mkp-5-pathways-in-ea-hy926-cells
#16
Hung-Chih Lin, Shih-Li Su, Wan-Chun Lin, Ai-Hsuan Lin, Ya-Chen Yang, Chong-Kuei Lii, Haw-Wen Chen
Andrographolide is a potent anti-inflammatory agent found in Andrographis paniculata. Endothelin 1 (ET-1) is an endothelium-derived vasoconstrictor with pro-inflammatory properties secreted in response to hypoxia. Mitogen-activated protein kinase phosphatase 5 (MKP-5) is a dual-specificity phosphatase that dephosphorylates threonine and tyrosine residues of MAPKs. We showed previously that hypoxia-induced HIF-1α expression and ET-1 secretion are dependent on p38 MAPK in EA.hy926 cells. Here, we investigate what role MKP-5 plays in andrographolide's inhibition of hypoxia-induced expression of HIF-1α and ET-1...
November 22, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29163807/macitentan-a-double-antagonist-of-endothelin-receptors-efficiently-impairs-migration-and-microenvironmental-survival-signals-in-chronic-lymphocytic-leukemia
#17
Rossana Maffei, Stefania Fiorcari, Tiziana Vaisitti, Silvia Martinelli, Stefania Benatti, Giulia Debbia, Davide Rossi, Patrizia Zucchini, Leonardo Potenza, Mario Luppi, Gianluca Gaidano, Silvia Deaglio, Roberto Marasca
The crosstalk between chronic lymphocytic leukemia (CLL) cells and tumor microenvironment is essential for leukemic clone maintenance, supporting CLL cells survival, proliferation and protection from drug-induced apoptosis. Over the past years, the role of several soluble factors involved in these processes has been studied. CLL cells express higher levels of endothelin 1 (ET-1) and ETA receptor as compared to normal B cells. Upon ET-1 stimulation, CLL cells improve their survival and proliferation and reduce their sensitivity to the phosphoinositide-3-kinase δ inhibitor idelalisib and to fludarabine...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29161233/swimming-but-not-vitamin-e-ameliorates-prothrombotic-state-and-hypofibrinolysis-in-a-rat-model-of-nonalcoholic-fatty-liver-disease
#18
Hussein F Sakr, Amr M Abbas, Mohamed A Haidara
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with a systemic procoagulant hypofibrinolysis state that is considered as a risk factor for microangiopathy and peripheral vascular diseases. Swimming exercise ameliorates the metabolic dysfunction in type 2 diabetes. Vitamin E is a natural antioxidant that reduces the risk of endothelial dysfunction in metabolic syndrome. The aim of the present study is to investigate the effect of combined swimming exercise with vitamin E on coagulation as well as blood fibrinolysis markers in rats with NAFLD...
November 21, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/29158679/treatment-of-pulmonary-hypertension-with-left-heart-disease-a-concise-review
#19
REVIEW
Anish Desai, Shilpa A Desouza
Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure ≥ 25 mmHg, as determined by right heart catheterization. Pulmonary arterial hypertension (PAH) can no longer be considered an orphan disease given the increase in awareness and availability of new drugs. PH carries with it a dismal prognosis and leads to significant morbidity and mortality. Symptoms can range from dyspnea, fatigue and chest pain to right ventricular failure and death. PH is divided into five groups by the World Health Organization (WHO), based on etiology...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/29140729/gene-expression-and-gene-associations-during-the-development-of-heart-failure-with-preserved-ejection-fraction-in-the-dahl-salt-sensitive-model-of-hypertension
#20
Jeffrey Yim, Hyokeun Cho, Simon W Rabkin
Gene expression and associations were examined in a model of heart failure with preserved ejection fraction (HFpEF), a condition with minimal effective treatment. Genes with at least two studies showing significant changes in Dahl rat with heart failure were examined by meta-analysis. Significantly increased in expression were iNOS, p47phox, ADM, ANP, OPN, ACE, MCP-1, GP91PHOX, ICAM-1, TGF-β1, CTGF, ET-1, p22phox, ETB, BNP, ETA, MMP13, Col1a1, MMP2, TIMP1, Col3a1, Il-1β, β-MHC, ECE1, MMP14, AGT, and MMP9...
November 15, 2017: Clinical and Experimental Hypertension: CHE
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