Adenoviral Delivery of VEGF121 Early in Pregnancy Prevents Spontaneous Development of Preeclampsia in BPH/5 Mice

Ashley K Woods; Darren S Hoffmann; Christine J Weydert; Scott D Butler; Yi Zhou; Ram V Sharma; Robin L Davisson

doi:10.1161/HYPERTENSIONAHA.110.160242

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Adenoviral Delivery of VEGF121 Early in Pregnancy Prevents Spontaneous Development of Preeclampsia in BPH/5 Mice

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Adenoviral Delivery of VEGF121 Early in Pregnancy Prevents Spontaneous Development of Preeclampsia in BPH/5 Mice

Ashley K Woods, Darren S Hoffmann, Christine J Weydert, Scott D Butler, Yi Zhou, Ram V Sharma and Robin L Davisson

Hypertension (Dallas, Tex. 1979), Vol.57(1), pp.94-102

01/2011

DOI: 10.1161/HYPERTENSIONAHA.110.160242

PMCID: PMC3026310

PMID: 21079047

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Abstract

An imbalance in circulating pro-angiogenic and anti-angiogenic factors is postulated to play a causal role in pre-eclampsia (PE). We have described an inbred mouse strain, BPH/5, which spontaneously develops a PE-like syndrome including late-gestational hypertension, proteinuria, and poor feto-placental outcomes. Here we tested the hypothesis that an angiogenic imbalance during pregnancy in BPH/5 mice leads to the development of PE-like phenotypes in this model. Similar to clinical findings, plasma from pregnant BPH/5 showed reduced levels of free vascular endothelial growth factor (VEGF) and placental growth factor (PGF) compared to C57BL/6 controls. This was paralleled by a marked decrease in VEGF protein and Pgf mRNA in BPH/5 placentae. Surprisingly, antagonism by the soluble form of the FLT1 receptor (sFLT1) did not appear to be the cause of this reduction, as sFLT1 levels were unchanged or even reduced in BPH/5 compared to controls. Adenoviral-mediated delivery of VEGF 121 (Ad-VEGF) via tail vein at e7.5 normalized both the plasma free VEGF levels in BPH/5 and restored the in vitro angiogenic capacity of serum from these mice. Ad-VEGF also reduced the incidence of fetal resorptions and prevented the late-gestational spike in blood pressure and proteinuria observed in BPH/5. These data underscore the importance of dysregulation of angiogenic factors in the pathogenesis of PE, and suggest the potential utility of early pro-angiogenic therapies in treating this disease.

placenta

sFLT1

hypertension

proteinuria

angiogenesis

PGF

Details

Title: Subtitle: Adenoviral Delivery of VEGF121 Early in Pregnancy Prevents Spontaneous Development of Preeclampsia in BPH/5 Mice
Creators: Ashley K Woods - Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853
Darren S Hoffmann - Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242
Christine J Weydert - Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA 52242
Scott D Butler - Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853
Yi Zhou - Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853
Ram V Sharma - Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853
Robin L Davisson - Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853
Resource Type: Journal article
Publication Details: Hypertension (Dallas, Tex. 1979), Vol.57(1), pp.94-102
DOI: 10.1161/HYPERTENSIONAHA.110.160242
PMID: 21079047
PMCID: PMC3026310
NLM abbreviation: Hypertension
ISSN: 0194-911X
eISSN: 1524-4563
Language: English
Date published: 01/2011
Academic Unit: Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology
Record Identifier: 9984025318202771

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