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 Hankins, Monica Longo, George Saade

Research output: Contribution to journalArticle

19 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume301
Issue number5
DOIs
StatePublished - Nov 2011

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Endothelial Growth Factors
Vascular Endothelial Growth Factor Receptor
Pre-Eclampsia
Vascular Endothelial Growth Factor A
Therapeutics
Blood Pressure
Pregnancy
Animal Models
Immunoglobulin Fc Fragments
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Thromboxanes
Nitroprusside
Phenylephrine
Vasodilator Agents
Carotid Arteries
Adenoviridae
Placenta
Acetylcholine
Blood Vessels

Keywords

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

ASJC Scopus subject areas

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

Cite this

Endothelial growth factor therapy improves preeclampsia-like manifestations in a murine model induced by overexpression of sVEGFR-1. / Mateus, Julio; Bytautiene, Egle; Lu, Fangxian; Tamayo, Esther H.; Betancourt, Ancizar; Hankins, Gary; Longo, Monica; Saade, George.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 301, No. 5, 11.2011.

Research output: Contribution to journalArticle

Mateus, Julio ; Bytautiene, Egle ; Lu, Fangxian ; Tamayo, Esther H. ; Betancourt, Ancizar ; Hankins, Gary ; Longo, Monica ; Saade, George. / Endothelial growth factor therapy improves preeclampsia-like manifestations in a murine model induced by overexpression of sVEGFR-1. In: American Journal of Physiology - Heart and Circulatory Physiology. 2011 ; Vol. 301, No. 5.
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AB - 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.

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