title: Adenosine and preeclampsia.
abstract: Adenosine is an endogenous nucleoside with pleiotropic effects in different physiological processes including circulation, renal blood flow, immune function, or glucose homeostasis. Changes in adenosine membrane transporters, adenosine receptors, and corresponding intracellular signalling network associate with development of pathologies of pregnancy, including preeclampsia. Preeclampsia is a cause of maternal and perinatal morbidity and mortality affecting 3-5% of pregnancies. Since the proposed mechanisms of preeclampsia development include adenosine-dependent biological effects, adenosine membrane transporters and receptors, and the associated signalling mechanisms might play a role in the pathophysiology of preeclampsia. Preeclampsia associates with increased adenosine concentration in the maternal blood and placental tissue, likely due to local hypoxia and ischemia (although not directly demonstrated), microthrombosis, increased catecholamine release, and platelet activation. In addition, abnormal expression and function of equilibrative nucleoside transporters is described in foetoplacental tissues from preeclampsia; however, the role of adenosine receptors in the aetiology of this disease is not well understood. Adenosine receptors activation may be related to abnormal trophoblast invasion, angiogenesis, and ischemia/reperfusion mechanisms in the placenta from preeclampsia. These mechanisms may explain only a low fraction of the associated abnormal transformation of spiral arteries in preeclampsia, triggering cellular stress and inflammatory mediators release from the placenta to the maternal circulation. Although increased adenosine concentration in preeclampsia may be a compensatory or adaptive mechanism favouring placental angiogenesis, a poor angiogenic state is found in preeclampsia. Thus, preeclampsia-associated complications might affect the cell response to adenosine due to altered expression and activity of adenosine receptors, membrane transporters, or cell signalling mechanisms. This review summarizes the evidence available on the potential involvement of the adenosine in the clinical, pathophysiology, and therapeutic features of preeclampsia.
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Seville E-41012, Spain. Electronic address: mdsalsoso@uc.cl.
authors.forename: Rocío
authors.initials: R
authors.lastname: Salsoso
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farías
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Cellular Signalling and Differentiation Laboratory (CSDL), Medical Technology School, Health Sciences Faculty, Universidad San Sebastian, Santiago 7510157, Chile.
authors.forename: Jaime
authors.initials: J
authors.lastname: Gutiérrez
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Metabolic Diseases Research Laboratory, Center of Research, Development and Innovation in Health - Aconcagua Valley, San Felipe Campus, School of Medicine, Faculty of Medicine, Universidad de Valparaíso, San Felipe 2172972, Chile.
authors.forename: Fabián
authors.initials: F
authors.lastname: Pardo
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.
authors.forename: Delia I
authors.initials: DI
authors.lastname: Chiarello
authors.affiliation: Department of Basic Science, Faculty of Science, Universidad de Bio-Bio, Chillán 3780000, Chile.
authors.forename: Fernando
authors.initials: F
authors.lastname: Toledo
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile.
authors.forename: Andrea
authors.initials: A
authors.lastname: Leiva
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Seville E-41012, Spain; Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Seville 41013, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mate
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Seville E-41012, Spain; Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Seville 41013, Spain.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Vázquez
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Seville E-41012, Spain; University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Queensland, Australia. Electronic address: sobrevia@med.puc.cl.
authors.forename: Luis
authors.initials: L
authors.lastname: Sobrevia
mesh_terms: D000241:Adenosine / Q000235:genetics* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000378:metabolism / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D018047:Receptors, Purinergic P1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D018047:Receptors, Purinergic P1; D000241:Adenosine
keywords: Adenosine; Adenosine receptor; Endothelium; Placenta; Preeclampsia; Trophoblast