title: Potential role of A2B adenosine receptors on proliferation/migration of fetal endothelium derived from preeclamptic pregnancies.
abstract: To investigate the functionality of A2B adenosine receptor (A2BAR) and the nitric oxide (NO) and vascular endothelial growth factor (VEGF) signaling pathway in the endothelial cell proliferation/migration during preeclampsia, we used human umbilical vein endothelial cells (HUVECs) isolated from normal pregnancies (n = 15) or pregnancies with preeclampsia (n = 15). Experiments were performed in presence or absence of the nonselective adenosine receptor agonist NECA, the A2BAR selective antagonist MRS-1754, and the nitric oxide synthase (NOS) inhibitor L-NAME. Results indicated that cells from preeclampsia exhibited a significant higher protein level of A2BAR and logEC50 for NECA-mediated proliferation than normotensive pregnancies. The stimulatory effect of NECA (10 μM, 24 h) on cell proliferation was prevented by MRS-1754 (5 nM) coincubation only in cells from normotensive pregnancies. Nevertheless, L-NAME (100 μM, 24 h) reduced the NECA-induced cell proliferation/migration in HUVEC from normal pregnancy; however in preeclampsia only NECA-induced cell proliferation was reduced by L-NAME. Moreover, NECA increased protein nitration and abundance of VEGF in cells from normal pregnancy and effect prevented by MRS-1754 coincubation. Nevertheless, in preeclampsia NECA did not affect the protein level of VEGF. In conclusion HUVECs from preeclampsia exhibit elevated protein level of A2BAR and impairment of A2BAR-mediated NO/VEGF signaling pathway.
authors.affiliation: Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Group of Research and Innovation in Vascular Health (GRIVAS Health), Department of Basic Sciences, Faculty of Sciences, Universidad del Bío-Bío, Chillán, Chile.
authors.forename: Jesenia
authors.initials: J
authors.lastname: Acurio
authors.affiliation: Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Group of Research and Innovation in Vascular Health (GRIVAS Health), Department of Basic Sciences, Faculty of Sciences, Universidad del Bío-Bío, Chillán, Chile.
authors.forename: Felipe
authors.initials: F
authors.lastname: Troncoso
authors.affiliation: Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Group of Research and Innovation in Vascular Health (GRIVAS Health), Department of Basic Sciences, Faculty of Sciences, Universidad del Bío-Bío, Chillán, Chile ; Obstetrics and Gynecology Department, Herminda Martin Clinical Hospital, Chillan, Chile.
authors.forename: Patricio
authors.identifier: 0000-0003-1053-448X
authors.initials: P
authors.lastname: Bertoglia
authors.affiliation: University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4006, Australia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Salomon
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Aguayo
authors.affiliation: University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4006, Australia ; Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynecology, Faculty of Medicine, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Sobrevia
authors.affiliation: Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Group of Research and Innovation in Vascular Health (GRIVAS Health), Department of Basic Sciences, Faculty of Sciences, Universidad del Bío-Bío, Chillán, Chile.
authors.forename: Carlos
authors.identifier: 0000-0001-7688-4621
authors.initials: C
authors.lastname: Escudero
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D002465:Cell Movement; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005333:Fetus / Q000378:metabolism* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011687:Purines / Q000494:pharmacology; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A
chemical_list: D000081:Acetamides; D000970:Antineoplastic Agents; C423842:N-(4-cyanophenyl)-2-(4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)-phenoxy)acetamide; D011687:Purines; D043704:Receptor, Adenosine A2B; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D019830:Adenosine-5'-(N-ethylcarboxamide)