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Alberto M Marra, Nicola Benjamin, Christina Eichstaedt, Andrea Salzano, Michele Arcopinto, Luna Gargani, Michele D Alto, Paola Argiento, Lorenzo Falsetti, Paolo Di Giosia, Andrea M Isidori, Francesco Ferrara, Eduardo Bossone, Antonio Cittadini, Ekkehard Grünig
During the last 15 years, a real "paradigm-shift" occurred, due to the development of PAH-targeted drugs, leading to crucial improvements in symptoms, exercise capacity, hemodynamics and outcome of PAH patients. In order to describe differences regarding epidemiology and therapy in PAH according to gender, we performed a review of the available literature in "PubMed" and "Web of Science" databases. In order to find relevant articles, we combined each of the following the keywords "pulmonary arterial hypertension", "gender", "sex", "men", "woman", "male", "female", "phosphodiesterase inhibitors", "endothelin receptor antagonists", "prostanoids"...
October 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
David F Woodward, Jenny W Wang, Ming Ni, Alex Bauer, Jose L Martos, Robert W Carling, Neil J Poloso
The purpose of these studies was to test the hypothesis that a selected polypharmacological approach for treating the prostanoid-mediated component of inflammatory diseases would produce a therapeutic effect superior to global inhibition of prostaglandin (PG) biosynthesis by aspirin-like drugs. The compound studied was AGN 211377, which had been previously shown to produce a superior effect on cytokine release from human macrophages compared with cyclooxygenase (COX) inhibitors. AGN 211377 antagonizes prostanoid prostaglandin D2 (DP)1, DP2, prostaglandin E2 (EP)1, EP4, prostaglandin F2α, and thromboxane A2 receptors but not anti-inflammatory EP2, prostaglandin I2, or EP3 receptors...
October 21, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
James A Shayman
Prostaglandins have been characterized as the metabolic products of arachidonic acid released from glycerophospholipids following hydrolysis by phospholipase A2s and enzymatic oxidation by the COX1 and COX2. In this issue of Cell Chemical Biology, Liu et al. (2016) examine the metabolism of 2-arachidonoyl-lyso-phosphatidylcholine and 2-arachidonoyl-lyso-phosphatidylethanolamine by COX2 and conversion to glycerolipid linked prostanoids, raising a series of interesting and important questions.
October 20, 2016: Cell Chemical Biology
Matías Hernández, Susana Wicz, Ricardo S Corral
BACKGROUND: Diverse cardiovascular signaling routes have been considered critical for Chagas cardiomyopathy caused by the protozoan parasite Trypanosoma cruzi. Along this line, T. cruzi infection and endothelin-1 (ET-1) have been shown to cooperatively activate the Ca(2+)/NFAT cascade in cardiomyocytes, leading to cyclooxygenase type 2 (COX-2) induction and increased release of prostanoids and prohypertrophic peptides. PURPOSE: To determine whether the well-known cardioprotective and anti-inflammatory effects of curcumin (Cur) could be helpful to interfere with this key machinery for pathogenesis of Chagas myocarditis...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
David F Woodward, Stacey L Wenthur, Tara L Rudebush, Shan Fan, Carol B Toris
PURPOSE: Since all prostanoid receptors affect intraocular pressure (IOP) and endogenous prostanoids are found in ocular tissues, the pressor effects of prostanoid antagonists were comprehensively evaluated. The absence of effects of most of these antagonists was not entirely anticipated. To ensure no false-negative results, ocular biodisposition studies were conducted. METHODS: Monkeys with laser-induced ocular hypertension were used to study antagonist effects on IOP...
October 20, 2016: Journal of Ocular Pharmacology and Therapeutics
H Olschewski, J Behr, H Bremer, M Claussen, P Douschan, M Halank, M Held, M M Hoeper, S Holt, H Klose, S Krüger, T J Lange, F Reichenberger, D Skowasch, S Ulrich, H Wilkens, W Seeger
The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH...
October 2016: Deutsche Medizinische Wochenschrift
K Bridget Brosnihan, Victor M Pulgar, Manish S Bharadwaj, Liomar A A Neves, Liliya M Yamaleyeva
BACKGROUND: Cyclooxygenase (COX)-derived prostanoids (PGE2, PGI2) are important contributors to the process of decidualization. Previous studies showed the presence of Ang-(1-7) in the primary and secondary decidualized zones of the implantation site at early pregnancy. Decreased concentrations of Ang-(1-7) were found in the decidualized uterus compared to the non-decidualized uterus of pseudopregnant rats, suggesting that low levels of Ang-(1-7) are required for successful decidualization at early pregnancy...
October 18, 2016: Reproductive Biology and Endocrinology: RB&E
Mayank Sardana, Matthew Moll, Harrison W Farber
Management of pulmonary arterial hypertension (PAH) remains challenging even in the contemporary era. Intravenous prostacyclin therapy, while associated with decreased mortality, has practical limitations and requires significant lifestyle modifications. The recently approved long-acting oral IP prostacyclin receptor agonist for treatment of PAH, selexipag, is a non-prostanoid agent that vasodilates, impacts remodeling (anti-proliferative), reduces endothelial cell dysfunction, inhibits platelet aggregation (anti-thrombotic), and increases right heart inotropy...
October 19, 2016: Expert Opinion on Drug Metabolism & Toxicology
Joohwee Kim, Vivek Vaish, Mingxiao Feng, Kevin Field, Ioulia Chatzistamou, Minsub Shim
Cyclooxygenase (COX) is a key enzyme in the biosynthesis of prostanoids, lipid signaling molecules that regulate various physiological processes. COX2, one of the isoforms of COX, is highly inducible in response to a wide variety of cellular and environmental stresses. Increased COX2 expression is thought to play a role in the pathogenesis of many age-related diseases. COX2 expression is also reported to be increased in the tissues of aged humans and mice, which suggests the involvement of COX2 in the aging process...
October 7, 2016: Aging
Gang Wu, Ah-Lim Tsai
Prostaglandin H synthase (PGHS) catalyzes the biosynthesis of PGG2 and PGH2, the precursor of all prostanoids, from arachidonic acid (AA). PGHS exhibits two enzymatic activities following a branched-chain radical mechanism: 1) a peroxidase activity (POX) which utilizes hydroperoxide through heme redox cycles to generate the critical Y385 tyrosyl radical for coupling both enzyme activities; 2) the cyclooxygenase (COX) activity which inserts two oxygen molecules into AA to generate endoperoxide/hydroperoxide PGG2 through a series of radical intermediates...
October 7, 2016: Protein and Peptide Letters
Halima Rakhila, Mahera Al-Akoum, Charles Doillon, Nicolas Lacroix-Pépin, Mathieu Leboeuf, Madeleine Lemyre, Ali Akoum, Marc Pouliot
CONTEXT: Angiogenesis is required for ectopic endometrial tissue growth. Our previous studies showed that prostaglandin F2α (PGF2α) biosynthetic enzymes and receptor were markedly elevated in endometriotic lesions and thatPGF2α is a potent angiogenic factor in endothelial cells. OBJECTIVE: We sought to determine whether or not the F-prostanoid receptor modulates angiogenesis in ectopic stromal cells. DESIGN: Release of angiogenic factors by ectopic endometrial stromal cell primary cultures stimulated with PGF2αand exposed to agents that target PGF2α signaling was assessed...
October 11, 2016: Journal of Clinical Endocrinology and Metabolism
Zuzanna Drebert, Mark MacAskill, Dahlia Doughty-Shenton, Karolien De Bosscher, Marc Bracke, Patrick W F Hadoke, Ilse M Beck
Angiogenesis is important in cancer progression and can be influenced by tumor-associated myofibroblasts. We addressed the hypothesis that glucocorticoids indirectly affect angiogenesis by altering the release of pro-angiogenic factors from colon cancer-derived myofibroblasts. Our study shows that glucocorticoids reduced prostanoids, urokinase-type plasminogen activator (uPA) and angiopoietin-like protein-2 (ANGPTL2) levels, but increased angiogenin (ANG) in supernatant from human CT5.3hTERT colon cancer-derived myofibroblasts...
October 4, 2016: Vascular Pharmacology
Lílian Cataldi Rodrigues, Adriana Secatto, Carlos A Sorgi, Naiara N Dejani, Alexandra I Medeiros, Morgana Kelly Borges Prado, Simone Gusmão Ramos, Richard D Cummings, Sean R Stowell, Lúcia Helena Faccioli, Marcelo Dias-Baruffi
Histoplasma capsulatum is a dimorphic fungus that develops a yeast-like morphology in host's tissue, responsible for the pulmonary disease histoplasmosis. The recent increase in the incidence of histoplasmosis in immunocompromised patients highlights the need of understanding immunological controls of fungal infections. Here, we describe our discovery of the role of endogenous galectin-1 (Gal-1) in the immune pathophysiology of experimental histoplasmosis. All infected wild-type (WT) mice survived while only 1/3 of Lgals1(-/-) mice genetically deficient in Gal-1 survived 30 days after infection...
2016: Mediators of Inflammation
Eamon P Mulvaney, Christine Shilling, Sarah B Eivers, Antoinette S Perry, Anders Bjartell, Elaine W Kay, R William Watson, B Therese Kinsella
The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa)...
September 26, 2016: Oncotarget
Joan Raouf, Nazmi Rafique, Michael Christopher Goodman, Helena Idborg, Filip Bergqvist, Richard N Armstrong, Per-Johan Jakobsson, Ralf Morgenstern, Linda Spahiu
INTRODUCTION: Prostaglandins are signaling molecules that regulate different physiological processes, involving allergic and inflammatory responses and cardiovascular control. They are involved in several pathophysiological processes, including inflammation and cancer. The inducible terminal enzyme, microsomal prostaglandin E synthase 1 (MPGES1), catalyses prostaglandin E2 production during inflammation. MPGES1 has therefore been intensively studied as a pharmaceutical target and many competitive inhibitors targeting its active site have been developed...
2016: PloS One
Manuel J Richter, Ralf Ewert, Christian Warnke, Henning Gall, Simon Classen, Friedrich Grimminger, Eckhard Mayer, Werner Seeger, Hossein-Ardeschir Ghofrani
BACKGROUND: In patients with severe pulmonary arterial hypertension, subcutaneous or catheter-based intravenous application of prostanoids carries a risk of local side effects or systemic infections, which limits their use and acceptance. Recently, a fully implantable pump for continuous application of intravenous treprostinil was approved in Germany. However, surgery is a major risk for patients with severe pulmonary arterial hypertension. The purpose of this study was to investigate the safety of a fully implantable pump inserted under local or general anesthesia in patients with severe pulmonary hypertension...
September 26, 2016: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
Sorin Tunaru, Ramesh Chennupati, Rolf M Nüsing, Stefan Offermanns
19(S)-hydroxy-eicosatetraenoic acid (19(S)-HETE) belongs to a family of arachidonic acid metabolites produced by cytochrome P450 enzymes, which play critical roles in the regulation of cardiovascular, renal and pulmonary functions. Although it has been known for a long time that 19(S)-HETE has vascular effects, its mechanism of action has remained unclear. In this study we show that 19(S)-HETE induces cAMP accumulation in the human megakaryoblastic leukemia cell line MEG-01. This effect was concentration-dependent with an EC50 of 520 nM, insensitive to pharmacological inhibition of COX-1/2 and required the expression of the G-protein Gs...
2016: PloS One
Martina Monti, Erika Terzuoli, Marina Ziche, Lucia Morbidelli
Cardiovascular diseases as atherosclerosis are associated to an inflammatory state of the vessel wall which is accompanied by endothelial dysfunction, and adherence and activation of circulating inflammatory cells. Hydrogen sulfide, a novel cardiovascular protective gaseous mediator, has been reported to exert anti-inflammatory activity. We have recently demonstrated that the SH containing ACE inhibitor zofenoprilat, the active metabolite of zofenopril, controls the angiogenic features of vascular endothelium through H2S enzymatic production by cystathionine gamma lyase (CSE)...
September 17, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Xuehong Liu, Zu-Yuan Qian, Fuchun Xie, Wei Fan, Jonathan W Nelson, Xiangshu Xiao, Sanjiv Kaul, Anthony P Barnes, Nabil J Alkayed
Epoxyeicosatrienoic acids (EETs) are potent vasodilators that play important roles in cardiovascular physiology and disease, yet the molecular mechanisms underlying the biological actions of EETs are not fully understood. Multiple lines of evidence suggest that the actions of EETs are in part mediated via G protein-coupled receptor (GPCR) signaling, but the identity of such a receptor has remained elusive. We sought to identify 14,15-EET-responsive GPCRs. A set of 105 clones were expressed in Xenopus oocyte and screened for their ability to activate cAMP-dependent chloride current...
September 17, 2016: Prostaglandins & Other Lipid Mediators
Akiko Suganami, Hiromichi Fujino, Iori Okura, Naoki Yanagisawa, Hajime Sugiyama, John W Regan, Yutaka Tamura, Toshihiko Murayama
Human D-type prostanoid (DP) and E-type prostanoid 2 (EP2) receptors are G protein-coupled receptors and are regarded as the most closely related receptors among prostanoid receptors because they are generated by tandem duplication. The DP receptor-cognate ligand, prostaglandin D2 (PGD2 ) has the ability to activate not only DP receptors, but also EP2 receptors. Likewise, the EP2 receptor-cognate ligand, prostaglandin E2 (PGE2 ) has the ability to activate DP receptors in addition to EP receptors in order to stimulate cAMP formation...
September 16, 2016: FEBS Journal
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