Endothelial growth factor therapy improves preeclampsia-like manifestations in a murine model induced by overexpression of sVEGFR-1

Julio Mateus, Egle Bytautiene, Fangxian Lu, Esther H. Tamayo, Ancizar Betancourt, Gary D.V. Hankins, Monica Longo, George R. Saade

Research output: Contribution to journalArticle

20 Scopus citations

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 G2a 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.

Original languageEnglish (US)
Pages (from-to)H1781-H1787
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number5
DOIs
StatePublished - Nov 1 2011

Keywords

  • Hypertension
  • Soluble vascular endothelial growth factor receptor 1
  • Vascular dysfunction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Endothelial growth factor therapy improves preeclampsia-like manifestations in a murine model induced by overexpression of sVEGFR-1'. Together they form a unique fingerprint.

  • Cite this