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Adenosine vascular

Mélanie Gaubert, Marion Marlinge, François Kerbaul, Noemie Resseguier, Marc Laine, Jennifer Cautella, Charlotte Cordier, Benjamin Colomb, Nathalie Kipson, Franck Thuny, Giovanna Mottola, Emmanuel Fenouillet, Jean Ruf, Franck Paganelli, Régis Guieu, Laurent Bonello
OBJECTIVES: To investigate whether adenosine A2A receptors lead to vasodilation and positive inotropic function under stimulation and whether they play a role in the control of blood pressure in patients with cardiogenic shock. DESIGN: Prospective observational study. SETTING: Monocentric, Hopital Nord, Marseille, France. SUBJECTS: Patients with cardiogenic shock (n = 16), acute heart failure (n = 16), and acute myocardial infarction (n = 16)...
June 19, 2018: Critical Care Medicine
Tinne C J Mertens, Ankit Hanmandlu, Ly Tu, Carole Phan, Scott D Collum, Ning-Yuan Chen, Tingting Weng, Jonathan Davies, Chen Liu, Holger K Eltzschig, Soma S K Jyothula, Keshava Rajagopal, Yang Xia, Ashrith Guha, Brian A Bruckner, Michael R Blackburn, Christophe Guignabert, Harry Karmouty-Quintana
Background: Pulmonary hypertension (PH) is a devastating and progressive disease characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and remodeling of the lung vasculature. Adenosine signaling through the ADORA2B receptor has previously been implicated in disease progression and tissue remodeling in chronic lung disease. In experimental models of PH associated with chronic lung injury, pharmacological or genetic inhibition of ADORA2B improved markers of chronic lung injury and hallmarks of PH...
2018: Frontiers in Physiology
Byambasuren Ganbaatar, Daiju Fukuda, Hotimah Masdan Salim, Sachiko Nishimoto, Kimie Tanaka, Yasutomi Higashikuni, Yoichiro Hirata, Shusuke Yagi, Takeshi Soeki, Masataka Sata
BACKGROUND AND AIMS: Ticagrelor reduces cardiovascular events in patients with acute coronary syndrome (ACS). Recent studies demonstrated the expression of P2Y12 on vascular cells including endothelial cells, as well as platelets, and suggested its contribution to atherogenesis. We investigated whether ticagrelor attenuates vascular dysfunction and inhibits atherogenesis in apolipoprotein E-deficient (apoe-/- ) mice. METHODS: Eight-week-old male apoe-/- mice were fed a western-type diet (WTD) supplemented with 0...
May 31, 2018: Atherosclerosis
M Verónica Donoso, M Jesús Mascayano, Inés M Poblete, J Pablo Huidobro-Toro
Since the mechanism of human diabetic peripheral neuropathy and vascular disease in type 1 diabetes mellitus remains unknown, we assessed whether sympathetic transmitter overflow is altered by this disease and associated to vascular dysfunction. Diabetes was induced by streptozotocin (STZ)-treatment and compared to vehicle-treated rats. Aliquots of the ex vivo perfused rat arterial mesenteric preparation, denuded of the endothelial layer, were collected to quantify analytically sympathetic nerve co-transmitters overflow secreted by the isolated mesenteries of both groups of rats...
2018: Frontiers in Pharmacology
Alicia J Jenkins, Paul Welsh, John R Petrie
PURPOSE OF REVIEW: We provide an overview of recent publications that extend clinically relevant knowledge relating to metformin's effects on lipids and atherosclerotic vascular disease and/or provide insights into the drug's mechanisms of action on the heart and vasculature. RECENT FINDINGS: We focus on original research in humans or in human tissues. Several recently completed randomized clinical trials have reported effects of metformin on surrogate measures of atherosclerotic vascular disease, including carotid-intima media thickness, vascular reactivity and calcification in people with Type 1 (T1D) and Type 2 (T2D) diabetes as well as nondiabetic dysglycaemia...
June 6, 2018: Current Opinion in Lipidology
Sanjay R Kharche, Aaron So, Fabio Salerno, Ting-Yim Lee, Chris Ellis, Daniel Goldman, Christopher W McIntyre
Dialysis prolongs life but augments cardiovascular mortality. Imaging data suggests that dialysis increases myocardial blood flow (BF) heterogeneity, but its causes remain poorly understood. A biophysical model of human coronary vasculature was used to explain the imaging observations, and highlight causes of coronary BF heterogeneity. Post-dialysis CT images from patients under control, pharmacological stress (adenosine), therapy (cooled dialysate), and adenosine and cooled dialysate conditions were obtained...
2018: Frontiers in Physiology
Jakub Jankowski, Heather M Perry, Christopher B Medina, Liping Huang, Junlan Yao, Amandeep Bajwa, Ulrike M Lorenz, Diane L Rosin, Kodi S Ravichandran, Brant E Isakson, Mark D Okusa
Background Pannexin1 (Panx1), an ATP release channel, is present in most mammalian tissues, but the role of Panx1 in health and disease is not fully understood. Panx1 may serve to modulate AKI; ATP is a precursor to adenosine and may function to block inflammation, or ATP may act as a danger-associated molecular pattern and initiate inflammation. Methods We used pharmacologic and genetic approaches to evaluate the effect of Panx1 on kidney ischemia-reperfusion injury (IRI), a mouse model of AKI. Results Pharmacologic inhibition of gap junctions, including Panx1, by administration of carbenoxolone protected mice from IRI...
June 4, 2018: Journal of the American Society of Nephrology: JASN
Meilin Liu, Xiaolong Chen, Henan Liu, Yu Di
Aim: The aim of the study was to investigate the signal transduction mechanism of Hedgehog-vascular endothelial growth factor in oxygen-induced retinopathy (OIR) and the effects of cyclopamine on OIR. Methods: An OIR model was established in C57BL/6J mice exposed to hyperoxia. Two hundred mice were randomly divided into a control group, an OIR group, an OIR-control group (treated with isometric phosphate-buffered saline by intravitreal injection), and a cyclopamine group (treated with cyclopamine by intravitreal injection), with 50 mice in each group...
2018: Drug Design, Development and Therapy
William A E Parker, Niclas Eriksson, Richard C Becker, Deepak Voora, Axel Åkerblom, Anders Himmelmann, Stefan K James, Lars Wallentin, Robert F Storey
In the PLATelet inhibition and patient Outcomes (PLATO) study, the P2Y12 inhibitors ticagrelor and clopidogrel were compared in the treatment of acute coronary syndromes (ACS). Ticagrelor was shown to reduce occurrence of the primary end point - a composite of death from vascular causes, myocardial infarction, or stroke - compared to clopidogrel. Ticagrelor's pleiotropic effects on reuptake of adenosine via inhibition of equilibrative nucleoside transporter 1 (ENT1) have been hypothesized to contribute to this...
May 31, 2018: Platelets
Naoto Fujii, Takeshi Nishiyasu, Ronald J Sigal, Pierre Boulay, Gregory W McGarr, Glen P Kenny
OBJECTIVE: We evaluated the hypothesis that aging attenuates muscarinic, nicotinic, and ATP- related cutaneous vasodilation. METHODS: In 11 young (24±4 years) and 11 older males (61±8 years), cutaneous vascular conductance (CVC) was assessed at three forearm skin sites that were infused with either: 1) methacholine (muscarinic receptor agonist, 5 doses: 0.0125, 0.25, 5, 100, 2000 mM), 2) nicotine (nicotinic receptor agonist, 5 doses: 1.2, 3.6, 11, 33, 100 mM), or 3) adenosine triphosphate (ATP) (purinergic receptor agonist, 5 doses: 0...
May 30, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Emese Balogh, Douglas J Veale, Trudy McGarry, Carl Orr, Zoltan Szekanecz, Chin-Teck Ng, Ursula Fearon, Monika Biniecka
BACKGROUND: In this study, we examined the effect of oxidative stress on cellular energy metabolism and pro-angiogenic/pro-inflammatory mechanisms of primary rheumatoid arthritis synovial fibroblast cells (RASFC) and human umbilical vein endothelial cells (HUVEC). METHODS: Primary RASFC and HUVEC were cultured with the oxidative stress inducer 4-hydroxy-2-nonenal (4-HNE), and extracellular acidification rate, oxygen consumption rate, mitochondrial function and pro-angiogenic/pro-inflammatory mechanisms were assessed using the Seahorse analyser, complex I-V activity assays, random mutation mitochondrial capture assays, enzyme-linked immunosorbent assays and functional assays, including angiogenic tube formation, migration and invasion...
May 29, 2018: Arthritis Research & Therapy
Elisabet Aliagas, Mariana Muñoz-Esquerre, Ester Cuevas, Oriol Careta, Daniel Huertas, Marta López-Sánchez, Ignacio Escobar, Jordi Dorca, Salud Santos
BACKGROUND: Extracellular adenosine triphosphate (ATP) is up-regulated in the airways of patients with chronic obstructive pulmonary disease (COPD), resulting in increased inflammation, bronchoconstriction, and cough. Although extracellular ATP levels are tightly controlled by nucleoside triphosphate diphosphohydrolase-1 (NTPDase1; also known as CD39) in the lungs, the role of CD39 in the pathology of COPD is unknown. We hypothesized that alterations in the expression and activity of CD39 could be part of the mechanisms for initiating and perpetuating the disease...
May 28, 2018: Respiratory Research
Sara Ariotti, Luis Ortega-Paz, Maarten van Leeuwen, Salvatore Brugaletta, Sergio Leonardi, K Martijn Akkerhuis, Stefano F Rimoldi, Gladys Janssens, Umberto Gianni, Jan C van den Berge, Alexios Karagiannis, Stephan Windecker, Marco Valgimigli
OBJECTIVES: The study sought to assess whether treatment with ticagrelor, as compared with prasugrel and clopidogrel, improves endothelium-dependent dilation throughout the course of the treatment and other vascular biomarkers, including systemic adenosine plasma levels. BACKGROUND: The in vivo off-target effects of ticagrelor in post-acute coronary syndrome (ACS) patients remain poorly characterized. METHODS: Fifty-four stable post-ACS patients were sequentially exposed to each of the 3 oral P2Y12 inhibitors following a 3-period balanced Latin square crossover design with 4 weeks per treatment in 5 European centers...
May 17, 2018: JACC. Cardiovascular Interventions
Kristian A Haanes, Alejandro Labastida-Ramírez, Kayi Y Chan, René de Vries, Brian Shook, Paul Jackson, Jimmy Zhang, Christopher M Flores, Alexander H J Danser, Carlos M Villalón, Antoinette MaassenVanDenBrink
BACKGROUND: Migraine is considered a neurovascular disorder, but its pathophysiological mechanisms are not yet fully understood. Adenosine has been shown to increase in plasma during migraine attacks and to induce vasodilation in several blood vessels; however, it remains unknown whether adenosine can interact with the trigeminovascular system. Moreover, caffeine, a non-selective adenosine receptor antagonist, is included in many over the counter anti-headache/migraine treatments. METHODS: This study used the rat closed cranial window method to investigate in vivo the effects of the adenosine A2A receptor antagonists with varying selectivity over A1 receptors; JNJ-39928122, JNJ-40529749, JNJ-41942914, JNJ-40064440 or JNJ-41501798 (0...
May 25, 2018: Journal of Headache and Pain
Andrew L Frelinger
Platelet-to-platelet aggregation is critical to the formation of hemostatic thrombi which limit bleeding following vascular injury and also contributes to obstructive thrombi in acute myocardial infarction, stroke, or other thrombotic diseases. Platelet aggregation is mediated by platelet surface glycoprotein (GP) IIb-IIIa (integrin αIIbβ3, CD41/61) on adjacent platelets. Upon platelet activation by adenosine diphosphate (ADP), thrombin, or other platelet agonists, GPIIb-IIIa undergoes conformational changes from a "resting" bent conformation to an "activated" extended conformation...
May 25, 2018: Platelets
Lowell Davis, James Musso, Divya Soman, Samantha Louey, Jonathan William Nelson, Sonnet S Jonker
Fetal anemia causes rapid and profound changes in cardiac structure and function, stimulating proliferation of the cardiac myocytes, expansion of the coronary vascular tree, and impairing early contraction and relaxation. While HIF-1α is sure to play a role, adenosine, a metabolic byproduct that increases coronary flow and growth, is implicated as a major stimulus for these adaptations. We hypothesized that genes involved in myocardial adenosine signaling would be up-regulated in chronically anemic fetuses, and that calcium handling genes would be down-regulated...
May 23, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Yinping Zhao, Ruolin Du, Tian Zhou, Dongchuan Yang, Yuhua Huang, Yi Wang, Junli Huang, Xiaoyi Ma, Fugui He, Juhui Qiu, Guixue Wang
An ideal vascular stent would both inhibit in-stent restenosis (ISR) and promote rapid re-endothelialization. In the current study, the performance of arsenic trioxide (ATO)-drug eluting stent (AES) is compared with the bare metal stent, poly-lactic-co-glycolic acid-coating metal stent, and rapamycin-drug eluting stent (RES). In vivo AES is shown to prevent neointimal hyperplasia more efficiently than the others when implanted into the carotid arteries of rabbits. Moreover, AES promotes endothelial cells proliferation and re-endothelialization more quickly than RES...
May 16, 2018: Advanced Healthcare Materials
Uttara Saran, Maria Guarino, Sarai Rodríguez, Cedric Simillion, Matteo Montani, Michelangelo Foti, Bostjan Humar, Marie V St-Pierre, Jean-François Dufour
Regular physical exercise has many beneficial effects, including antitumor properties, and is associated with a reduced risk of developing hepatocellular carcinoma (HCC). Less is known about the impact of exercise on HCC growth and progression. Here, we investigated the effects of exercise on HCC progression and assessed whether any beneficial effects would be evident under sorafenib treatment and could be mimicked by metformin. American Cancer Institute rats with orthotopic syngeneic HCC derived from Morris Hepatoma-3924A cells were randomly assigned to exercise (Exe) and sedentary groups, or sorafenib±Exe groups or sorafenib±metformin groups...
May 2018: Hepatology communications
Mafalda Bessa-Gonçalves, Bruno Bragança, Eduardo Martins-Dias, Paulo Correia-de-Sá, Ana Patrícia Fontes-Sousa
Pulmonary arterial hypertension (PAH) is a maladaptive disorder characterized by increased pulmonary vascular resistance leading to right ventricular failure and death. Adenosine released by injured tissues, such as the lung and heart, influences tissue remodeling through the activation of adenosine receptors. Evidence regarding activation of the low-affinity A2B AR by adenosine points towards pivotal roles of this receptor in processes associated with both acute and chronic lung diseases. Conflicting results exist concerning the beneficial or detrimental roles of the A2B 'biased' receptor in right ventricular failure secondary to PAH...
May 7, 2018: Drug Discovery Today
Venkateswara Reddy Gogulamudi, Jinjin Cai, Lisa A Lesniewski
Cardiovascular diseases (CVDs) remain the leading causes of death in the US, and advancing age is a primary risk factor. Impaired endothelium dependent dilation and increased stiffening of the arteries with aging are independent predictors of CVD. Increased tissue and systemic oxidative stress and inflammation underlie this age-associated arterial dysfunction. Calorie restriction (CR) is the most powerful intervention known to increase lifespan and improve age-related phenotypes, including arterial dysfunction...
May 10, 2018: Journal of Applied Physiology
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