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https://www.readbyqxmd.com/read/28195470/total-synthesis-confirms-the-molecular-structure-proposed-for-oxidized-levuglandin-d2
#1
Yu-Shiuan Cheng, Wenyuan Yu, Yunfeng Xu, Robert G Salomon
Levuglandins (LG)D2 and LGE2 are γ-ketoaldehyde levulinaldehyde derivatives with prostanoid side chains produced by spontaneous rearrangement of the endoperoxide intermediate PGH2 in the biosynthesis of prostaglandins. Covalent adduction of LGs with the amyloid peptide Aβ1-42 promotes formation of the type of oligomers that have been associated with neurotoxicity and are a pathologic hallmark of Alzheimer's disease. Within 1 min of their generation during the production of PGH2 by cyclooxygenation of arachidonic acid, LGs are sequestered by covalent adduction to proteins...
February 14, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28192127/long-term-treatment-with-nandrolone-decanoate-impairs-mesenteric-vascular-relaxation-in-both-sedentary-and-exercised-female-rats
#2
Izabela F Caliman, Cristian S Bernabe, Antônio F de Melo, Girlândia A Brasil, Andrews M do Nascimento, Ewelyne M de Lima, Suely G Figueiredo, Tadeu U de Andrade, Nazaré S Bissoli
Nandrolone Decanoate (ND) is an Anabolic Androgenic Steroid (AAS) that under abusive regimen can lead to multiple physiological adverse effects. Studies of AAS-mediated cardiovascular (CV) alterations were mostly taken from male subjects, even though women are also susceptible to the effects of AAS and gender-specific differences in susceptibility to vascular diseases exist. Here we investigate ND-induced vascular reactivity alterations in both sedentary and exercised female rats and whether these alterations depend on endothelium-derived factors...
February 9, 2017: Steroids
https://www.readbyqxmd.com/read/28190787/comparison-of-hemodynamic-parameters-in-treatment-na%C3%A3-ve-and-pre-treated-patients-with-pulmonary-arterial-hypertension-in-the-randomized-phase-iii-patent-1-study
#3
Nazzareno Galiè, Friedrich Grimminger, Ekkehard Grünig, Marius M Hoeper, Marc Humbert, Zhi-Cheng Jing, Anne M Keogh, David Langleben, Lewis J Rubin, Arno Fritsch, Neil Davie, Hossein-Ardeschir Ghofrani
BACKGROUND: Detailed hemodynamic data from the phase III PATENT-1 study of riociguat in patients with pulmonary arterial hypertension (PAH) were investigated. METHODS: Patients with PAH who were treatment naïve or pre-treated with endothelin receptor antagonists or non-intravenous prostanoids were randomly assigned to riociguat up to 2.5 mg 3 times a day or placebo. Hemodynamic parameters were assessed at baseline and week 12. RESULTS: Riociguat significantly decreased pulmonary vascular resistance in treatment-naïve (n = 221; least squares [LS] mean difference -266 dyne∙sec∙cm(-5) [95% confidence interval (CI) -357 to -175; p < 0...
December 24, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28177721/mechanisms-of-nicotine-induced-cutaneous-vasodilation-and-sweating-in-young-adults-roles-for-k-sub-ca-sub-k-sub-atp-sub-and-k-sub-v-sub-channels-nitric-oxide-and-prostanoids
#4
Naoto Fujii, Jeffrey C Louie, Brendan D McNeely, Tatsuro Amano, Takeshi Nishiyasu, Glen P Kenny
We evaluated the influence of K<sup>+</sup> channels [i.e., Ca<sup>2+</sup>-activated K<sup>+</sup> (K<sub>Ca</sub>), ATP-sensitive K<sup>+</sup> (K<sub>ATP</sub>), and voltage-gated K<sup>+</sup> (K<sub>V</sub>) channels] and key enzymes [(nitric oxide synthase (NOS) and cyclooxygenase (COX)] on nicotine-induced cutaneous vasodilation and sweating. Using intradermal microdialysis, we evaluated forearm cutaneous vascular conductance (CVC) and sweat rate in two separate protocols...
January 10, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28174191/augmentation-of-muscle-blood-flow-by-ultrasound-cavitation-is-mediated-by-atp-and-purinergic-signaling
#5
J Todd Belcik, Brian P Davidson, Aris Xie, Melinda D Wu, Mrinal Yadava, Yue Qi, Sherry Liang, Chae Ryung Chon, Azzdine Y Ammi, Joshua Field, Leanne Harmann, William M Chilian, Joel Linden, Jonathan R Lindner
BACKGROUND: - Augmentation of tissue blood flow by therapeutic ultrasound is thought to rely on convective shear. Microbubble contrast agents that undergo ultrasound-mediated cavitation markedly amplify these effects. We hypothesized that purinergic signalling is responsible for shear-dependent increases in muscle perfusion during therapeutic cavitation. METHODS: -Unilateral exposure of the proximal hindlimb of mice (with or without ischemia produced by iliac ligation) to therapeutic ultrasound (1...
February 7, 2017: Circulation
https://www.readbyqxmd.com/read/28165064/role-of-e-type-prostaglandin-receptor-ep3-in-the-vasoconstrictor-activity-evoked-by-prostacyclin-in-thromboxane-prostanoid-receptor-deficient-mice
#6
Zhenhua Li, Yingzhan Zhang, Bin Liu, Wenhong Luo, Hui Li, Yingbi Zhou
Prostacyclin, also termed as prostaglandin I2 (PGI2), evokes contraction in vessels with limited expression of the prostacyclin receptor. Although the thromboxane-prostanoid receptor (TP) is proposed to mediate such a response of PGI2, other unknown receptor(s) might also be involved. TP knockout (TP(-/-)) mice were thus designed and used to test the hypothesis. Vessels, which normally show contraction to PGI2, were isolated for functional and biochemical analyses. Here, we showed that the contractile response evoked by PGI2 was indeed only partially abolished in the abdominal aorta of TP(-/-) mice...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28161224/cox-2-inhibitor-prevents-tumor-induced-down-regulation-of-classical-dc-lineage-specific-transcription-factor-zbtb46-resulting-in-immunocompetent-dc-and-decreased-tumor-burden
#7
Vipul K Pandey, Prayag J Amin, Bhavani S Shankar
The interaction between the immune and tumor cells in the microenvironment is an important factor deciding the progression of cancer. Though many of the soluble mediators in the microenvironment that mediate immunosuppression are known, the mechanism by which the tumor affects the distal progenitors is not known. We report that the tumor derived prostanoids down regulated classical dendritic cells DC (cDC) lineage specific transcription factor Zbtb46 in the progenitor cells which affects its differentiation...
February 1, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28150299/role-of-pvat-on-coronary-atherosclerosis-and-vein-graft-patency-friend-or-foe
#8
REVIEW
M S Fernández Alfonso, M Gil-Ortega, I Aranguez, D Souza, M Dreifaldt, B Somoza, M R Dashwood
Perivascular adipose tissue (PVAT) releases multiple factors and adipokines with paracrine effects on both vascular structure and function. This influence is variable depending on regional differences in PVAT among blood vessels and with changes in adiposity. Considerable evidence demonstrates the association between coronary PVAT and the development and progression of coronary artery disease, associated with inflammation, oxidative stress, angiogenesis, vascular remodeling and blood clotting. However, PVAT also has a protective role on vascular grafts, especially the no-touch saphenous vein, in patients undergoing coronary artery bypass...
February 1, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28123585/host-knockout-of-e-prostanoid-2-receptors-reduces-tumor-growth-and-causes-major-alterations-of-gene-expression-in-prostaglandin-e2-producing-tumors
#9
Annika Gustafsson Asting, Britt-Marie Iresjö, Camilla Nilsberth, Ulrika Smedh, Kent Lundholm
Prostaglandin E2 (PGE2) is elevated in a variety of malignant tumors and has been shown to affect several hallmarks of cancer. Accordingly, the PGE2 receptor, E-prostanoid 2 (EP2), has been reported to be associated with patient survival and reduced tumor growth in EP2-knockout mice. Thus, the aim of the present study was to screen for major gene expression alterations in tumor tissue growing in EP2-knockout mice. EP2-knockout mice were bred and implanted with EP2 receptor-expressing and PGE2-producing epithelial-like tumors...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28120127/a-novel-prostanoid-ep1-receptor-antagonist-ono-8539-reduces-acid-induced-heartburn-symptoms-in-healthy-male-volunteers-a-randomized-clinical-trial
#10
Takashi Kondo, Hiroo Sei, Takahisa Yamasaki, Toshihiko Tomita, Yoshio Ohda, Tadayuki Oshima, Hirokazu Fukui, Jiro Watari, Hiroto Miwa
BACKGROUND: Patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) have unmet clinical needs. Recently, we reported that esophageal prostaglandin E2 (PGE2) plays a crucial role in the generation of heartburn. In the present study, we focused on the PGE2 receptor, EP1, and investigated the effects of ONO-8539, a novel EP1 receptor antagonist, on heartburn symptoms in healthy male volunteers. METHODS: This prospective, double-blind, placebo-controlled, two-period crossover study was performed in 20 healthy male subjects...
January 24, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28108419/regulation-of-protein-kinase-c-related-kinase-prk-signalling-by-the-tp%C3%AE-and-tp%C3%AE-isoforms-of-the-human-thromboxane-a2-receptor-implications-for-thromboxane-and-androgen-dependent-neoplastic-and-epigenetic-responses-in-prostate-cancer
#11
Aine G O'Sullivan, Eamon P Mulvaney, B Therese Kinsella
The prostanoid thromboxane (TX) A2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA2/TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA2-TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC...
January 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28108308/role-of-cyclooxygenase-in-the-vascular-response-to-locally-delivered-acetylcholine-in-caucasian-and-african-descent-individuals
#12
Matthew J Maley, James R House, Michael J Tipton, Clare M Eglin
INTRODUCTION: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury (NFCI) compared with Caucasian individuals (CAU). Vasodilatation to acetylcholine (ACh) is lower in AFD compared with CAU in the non-glabrous foot and finger skin sites; the reason for this is unknown. Prostanoids are responsible, in part, for the vasodilator response to ACh, however it is not known whether the contribution differs between ethnicities. METHODS: 12 CAU and 12 AFD males received iontophoresis of ACh (1 w/v%) on non-glabrous foot and finger skin sites following placebo and then aspirin (600mg, single blinded)...
January 17, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28090295/an-advanced-protocol-driven-transition-from-parenteral-prostanoids-to-inhaled-trepostinil-in-pulmonary-arterial-hypertension
#13
Ronald Oudiz, Manyoo Agarwal, Franz Rischard, Teresa De Marco
Patients with pulmonary arterial hypertension (PAH) often require parenteral prostanoids to improve symptoms and signs of PAH. Complications of parenteral prostanoids-such as catheter-related infections and intolerable adverse effects-may develop, prompting transition to inhaled prostanoids. We report a prospective, protocol-driven transition from parenteral prostanoids to inhaled prostanoids with monitoring of exercise gas exchange and acute hemodynamics. Three PAH centers recruited patients transitioning from parenteral prostanoids to inhaled trepostinil...
December 2016: Pulmonary Circulation
https://www.readbyqxmd.com/read/28086956/differential-expression-of-e-type-prostanoid-receptors-2-and-4-in-microglia-stimulated-with-lipopolysaccharide
#14
Ester Bonfill-Teixidor, Amaia Otxoa-de-Amezaga, Miriam Font-Nieves, M Glòria Sans-Fons, Anna M Planas
BACKGROUND: Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP receptors in glial activation in response to an inflammatory challenge induced by LPS. METHODS: Cultures of mouse microglia or astroglia cells were treated with LPS in the presence or absence of COX-2 inhibitors, and the production of PGE2 was measured by ELISA...
January 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28072531/discovery-of-2-1r-4r-4-4-chlorophenyl-phenyl-carbamoyl-oxy-methyl-cyclohexyl-methoxy-acetate-ralinepag-an-orally-active-prostacyclin-receptor-agonist-for-the-treatment-of-pulmonary-arterial-hypertension
#15
Thuy-Anh Tran, Bryan Kramer, Young-Jun Shin, Pureza Vallar, P Douglas Boatman, Ning Zou, Carleton R Sage, Tawfik Gharbaoui, Ashwin Krishnan, Biman Pal, Sagar R Shakya, Antonio Garrido Montalban, John W Adams, Juan Ramirez, Dominic P Behan, Anna Shifrina, Anthony Blackburn, Tina Leakakos, Yunqing Shi, Michael Morgan, Abu Sadeque, Weichao Chen, David J Unett, Ibragim Gaidarov, Xiaohua Chen, Steve Chang, Hsin-Hui Shu, Shiu-Feng Tung, Graeme Semple
The design and synthesis of a new series of potent non-prostanoid IP receptor agonists that showed oral efficacy in the rat monocrotaline model of pulmonary arterial hypertension (PAH) are described. Detailed profiling of a number of analogues resulted in the identification of 5c (ralinepag) that has good selectivity in both binding and functional assays with respect to most members of the prostanoid receptor family and a more modest 30- to 50-fold selectivity over the EP3 receptor. In our hands, its potency and efficacy are comparable or superior to MRE269 (the active metabolite of the clinical compound NS-304) with respect to in vitro IP receptor dependent cAMP accumulation assays...
February 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28069828/lpa1-receptor-mediated-thromboxane-a2-release-is-responsible-for-lysophosphatidic-acid-induced-vascular-smooth-muscle-contraction
#16
Péter Tibor Dancs, Éva Ruisanchez, Andrea Balogh, Cecília Rita Panta, Zsuzsanna Miklós, Rolf M Nüsing, Junken Aoki, Jerold Chun, Stefan Offermanns, Gábor Tigyi, Zoltán Benyó
Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA1, LPA2, LPA4, and LPA6 In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and the LPA1-3 agonist VPC31143 induced dose-dependent vasoconstriction...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28068359/docosahexaenoic-acid-supplemented-diet-influences-the-orchidectomy-induced-vascular-dysfunction-in-rat-mesenteric-arteries
#17
Diva M Villalpando, Rocío Navarro, Lara Del Campo, Carlota Largo, David Muñoz, María Tabernero, Ramiro Baeza, Cristina Otero, Hugo S García, Mercedes Ferrer
Over the past few decades, the cardiovascular benefits of a high dietary intake of long-chain polyunsaturated fatty acids (PUFAs), like docosahexaenoic acid (DHA), have been extensively studied. However, many of the molecular mechanisms and effects exerted by PUFAs have yet to be well explained. The lack of sex hormones alters vascular tone, and we have described that a DHA-supplemented diet to orchidectomized rats improve vascular function of the aorta. Based on these data and since the mesenteric artery importantly controls the systemic vascular resistance, the objective of this study was to analyze the effect of a DHA-supplemented diet on the mesenteric vascular function from orchidectomized rats...
2017: PloS One
https://www.readbyqxmd.com/read/28067255/serelaxin-treatment-reverses-vascular-dysfunction-and-left-ventricular-hypertrophy-in-a-mouse-model-of-type-1-diabetes
#18
Hooi Hooi Ng, Chen Huei Leo, Darnel Prakoso, Chengxue Qin, Rebecca H Ritchie, Laura J Parry
Serelaxin prevents endothelial dysfunction in the mouse aorta ex vivo and inhibits apoptosis in cardiomyocytes under acute hyperglycaemia. Less is known about the effects of serelaxin in an in vivo mouse model of diabetes. Therefore, we tested the hypothesis in streptozotocin (STZ)-treated mice that serelaxin is able to reverse diabetes-induced vascular dysfunction and cardiac remodelling. Mice were divided into citrate buffer + placebo, STZ + placebo and STZ + serelaxin (0.5 mg/kg/d, 2 weeks) groups...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065721/the-key-residue-within-the-second-extracellular-loop-of-human-ep3-involved-in-selectively-turning-down-pge2-and-retaining-pge1-mediated-signaling-in-live-cells
#19
Hironari Akasaka, Natasha Thaliachery, Xianghai Zheng, Marissa Blumenthal, Sameer Nikhar, Emma E Murdoch, Qinglan Ling, Ke-He Ruan
Key residues and binding mechanisms of PGE1 and PGE2 on prostanoid receptors are poorly understood due to the lack of X-ray structures for the receptors. We constructed a human EP3 (hEP3) model through integrative homology modeling using the X-ray structure of the β2-adrenergic receptor transmembrane domain and NMR structures of the thromboxane A2 receptor extracellular loops. PGE1 and PGE2 docking into the hEP3 model showed differing configurations within the extracellular ligand recognition site. While PGE2 could form possible binding contact with S211, PGE1 is unable to form similar contacts...
January 5, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28062696/prostaglandin-e2-inhibition-of-il-27-production-in-murine-dendritic-cells-a-novel-mechanism-that-involves-irf1
#20
Kirsten M Hooper, Jui-Hung Yen, Weimin Kong, Kate M Rahbari, Ping-Chang Kuo, Ana M Gamero, Doina Ganea
IL-27, a multifunctional cytokine produced by APCs, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well studied, much less is known about the factors that negatively impact IL-27 expression. PGE2, a major immunomodulatory prostanoid, acts as a proinflammatory agent in several models of inflammatory/autoimmune disease, promoting primarily Th17 development and function...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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