title: Role of equilibrative adenosine transporters and adenosine receptors as modulators of the human placental endothelium in gestational diabetes mellitus.
abstract: Gestational diabetes mellitus (GDM) is a diseases that alters human placenta macro and microvascular reactivity as a result of endothelial dysfunction. The human placenta is a highly vascularized organ which lacks innervation, so blood flux is governed by locally released vasoactive molecules, including the endogenous nucleoside adenosine and the free radical nitric oxide (NO). Altered adenosine metabolism and uptake by the endothelium leads to increased NO synthesis which then turns-off the expression of genes coding for a family of nucleoside membrane transporters belonging to equilibrative nucleoside transporters, particularly isoforms 1 (hENT1) and 2 (hENT2). This mechanism leads to increased extracellular adenosine and, as a consequence, activation of adenosine receptors to further sustain a tonic activation of NO synthesis. This is a phenomenon that seems operative in the placental macro and microvascular endothelium in GDM. We here summarize the findings available in the literature regarding these mechanisms in the human feto-placental circulation. This phenomenon is altered in the feto-placental vasculature, which could be crucial for understanding GDM deleterious effects in fetal growth and development.
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, P.O. Box 114-D, Santiago, Chile. Electronic address: fpardo@med.puc.cl.
authors.forename: F
authors.initials: F
authors.lastname: Pardo
authors.forename: P
authors.initials: P
authors.lastname: Arroyo
authors.forename: C
authors.initials: C
authors.lastname: Salomón
authors.forename: F
authors.initials: F
authors.lastname: Westermeier
authors.forename: R
authors.initials: R
authors.lastname: Salsoso
authors.forename: T
authors.initials: T
authors.lastname: Sáez
authors.forename: E
authors.initials: E
authors.lastname: Guzmán-Gutiérrez
authors.forename: A
authors.initials: A
authors.lastname: Leiva
authors.forename: L
authors.initials: L
authors.lastname: Sobrevia
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D016640:Diabetes, Gestational / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D033705:Equilibrative Nucleoside Transport Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D055806:Microvessels / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism; D021041:Placental Circulation; D011247:Pregnancy; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015290:Second Messenger Systems
chemical_list: D033705:Equilibrative Nucleoside Transport Proteins; D018047:Receptors, Purinergic P1; D009569:Nitric Oxide; D000241:Adenosine
keywords: Adenosine; Endothelium; Gestational diabetes; Insulin; Placenta