title: Adenosine A2Areceptor regulates expression of vascular endothelial growth factor in feto-placental endothelium from normal and late-onset pre-eclamptic pregnancies.
abstract: We aim to investigate whether A2A/nitric oxide-mediated regulation of vascular endothelial growth factor (VEGF) expression is impaired in feto-placental endothelial cells from late-onset pre-eclampsia. Cultures of human umbilical vein endothelial cells (HUVECs) and human placental microvascular endothelial cells (hPMECs) from normal and pre-eclamptic pregnancies were used. Assays by using small interference RNA (siRNA) for A2Awere performed, and transfected cells were used for estimation of messenger RNA (mRNA) levels of VEGF, as well as for cell proliferation and angiogenesis in vitro. CGS-21680 (A2Aagonist, 24 h) increases HUVEC and hPMEC proliferation in a dose response manner. Furthermore, similar to CGS-21680, the nitric oxide donor, S-nitroso-N-acetyl-penicillamine oxide (SNAP), increased cell proliferation in a dose response manner (logEC5010-9.2M). In hPMEC, CGS-21680 increased VEGF protein levels in both normal (∼1.5-fold) and pre-eclamptic pregnancies (∼1.2-fold), an effect blocked by the A2Aantagonist, ZM-241385 (10-5M) and the inhibitor of NO synthase, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). Subsequently, SNAP partially recovered cell proliferation and in vitro angiogenesis capacity of cells from normal pregnancies exposed to siRNA for A2A. CGS-21680 also increased (∼1.5-fold) the level of VEGF mRNA in HUVEC from normal pregnancies, but not in pre-eclampsia. Additionally, transfection with siRNA for A2Adecrease (∼30 %) the level of mRNA for VEGF in normal pregnancy compared to untransfected cells, an effect partially reversed by co-incubation with SNAP. The A2A-NO-VEGF pathway is present in endothelium from microcirculation and macrocirculation in both normal and pre-eclamptic pregnancies. However, NO signaling pathway seems to be impaired in HUVEC from pre-eclampsia.
authors.affiliation: Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Department of Basic 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), Department of Basic Sciences, Universidad del Bío-Bío, Chillán, Chile.
authors.forename: Kurt
authors.initials: K
authors.lastname: Herlitz
authors.affiliation: Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Department of Basic Sciences, Universidad del Bío-Bío, Chillán, Chile.
authors.forename: Felipe
authors.initials: F
authors.lastname: Troncoso
authors.affiliation: Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.|Group of Research and Innovation in Vascular Health (GRIVAS Health), Chillan, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Aguayo
authors.affiliation: Obstetric and Gynecology Department, Hospital Clinico Herminda Martin, Chillán, Chile, Universidad Católica de la Santísima Concepción, Concepción, Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Bertoglia
authors.affiliation: Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Department of Basic Sciences, Universidad del Bío-Bío, Chillán, Chile. cescudero@ubiobio.cl.|Group of Research and Innovation in Vascular Health (GRIVAS Health), Chillan, Chile. cescudero@ubiobio.cl.
authors.forename: Carlos
authors.initials: C
authors.lastname: Escudero
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D042461:Vascular Endothelial Growth Factor A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D009569:Nitric Oxide; D000241:Adenosine
keywords: A2A; Adenosine; Angiogenesis; Nitric oxide; Pre-eclampsia; VEGF