title: Endothelial growth factor therapy improves preeclampsia-like manifestations in a murine model induced by overexpression of sVEGFR-1.
abstract: This study examines the effects of VEGF-121 therapy in an animal model of preeclampsia induced by overexpression of soluble VEGF receptor 1 (sVEGFR-1). At day 8 of gestation, CD-1 mice were implanted with subcutaneous osmotic pumps containing either VEGF-121 or vehicle and fitted with telemetric blood pressure (BP) catheters for continuous BP monitoring (days 8-18 of gestation). On day 9, the animals in the VEGF-121 group were randomly allocated for injection with adenovirus carrying sVEGFR-1 or the murine immunoglobulin G2α Fc fragment (mFc) as virus control (Adv-sVEGFR-1; Adv-mFc). Animals in the vehicle group were injected with Adv-sVEGFR-1. On day 18, mice were euthanized, placentas and pups weighted, carotid arteries isolated, and their responses studied in vitro using a wire myograph for isometric tension recording. In mice overexpressing sVEGFR-1, treatment with VEGF-121 significantly reduced BP from days 10 to 18 of gestation compared with that of vehicle. VEGF-sVEGFR-1 animals had significantly higher vasorelaxant response to sodium nitroprusside and significantly lower contractile response to the thromboxane agonist (U-46619) compared with that of the vehicle-sVEGFR-1 mice. Phenylephrine and acetylcholine responses did not significantly vary between the VEGF-sVEGFR-1 and the vehicle-sVEGFR-1 mice. Average pup weight was significantly lower in the vehicle-sVEGFR-1 group compared with the VEGF-sVEGFR-1 and VEGF-mFc groups. In conclusion, VEGF-121 therapy attenuates vascular dysfunction and diminishes intrauterine growth abnormality in an animal model of preeclampsia induced by overexpression of sVEGFR-1. Modulation of VEGF pathway turns into a promising therapeutic approach of preeclampsia.
authors: Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, Texas, USA. jfmateus@utmb.edu
authors: Julio
authors: J
authors: Mateus
authors: Egle
authors: E
authors: Bytautiene
authors: Fangxian
authors: F
authors: Lu
authors: Esther H
authors: EH
authors: Tamayo
authors: Ancizar
authors: A
authors: Betancourt
authors: Gary D V
authors: GD
authors: Hankins
authors: Monica
authors: M
authors: Longo
authors: George R
authors: GR
authors: Saade
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D020567:Fetal Weight; D005822:Genetic Vectors; D005865:Gestational Age; D015918:Infusion Pumps, Implantable; D055104:Infusions, Subcutaneous; D051379:Mice; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011994:Recombinant Proteins / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1