Document Detail


Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia.
MedLine Citation:
PMID:  17724276     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inhibitors of angiogenic factors are known to be upregulated, and their levels increase in the maternal circulation before the onset of preeclampsia. We reproduced a previously characterized model of preeclampsia by adenoviral overexpression of the soluble vascular endothelial growth factor (VEGF) receptor sFlt-1 (also referred to as sVEGFR-1) in pregnant and nonpregnant Sprague-Dawley rats. Animals were treated with VEGF121 at 0, 100, 200, or 400 microg/kg once or twice daily (n=8 per group; 64 total) and compared with normal control animals (n=4 per group) by examination of systolic blood pressure, urinary albumin and creatinine, renal histopathology, and glomerular gene expression profiling. sFlt-1 expression induced hypertension with proteinuria and glomerular endotheliosis and significant changes in gene expression. VEGF121 treatment alleviated these symptoms and reversed 125 of 268 sFlt-1-induced changes in gene expression. VEGF121 had beneficial effects in this rat model of preeclampsia without apparent harm to the fetus. Further study of VEGF121 as a potential therapeutic agent for preeclampsia is warranted.
Authors:
Zhihe Li; Ying Zhang; Jing Ying Ma; Ann M Kapoun; Qiming Shao; Irene Kerr; Andrew Lam; Gilbert O'Young; Frederick Sannajust; Peter Stathis; George Schreiner; S Ananth Karumanchi; Andrew A Protter; N Stephen Pollitt
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-08-27
Journal Detail:
Title:  Hypertension     Volume:  50     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-20     Completed Date:  2007-10-29     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  686-92     Citation Subset:  IM    
Affiliation:
Scios Inc., Fremont, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Gene Expression Regulation / drug effects
Hypertension / drug therapy*,  physiopathology
Kidney / drug effects*,  metabolism,  pathology*
Pre-Eclampsia / drug therapy*,  physiopathology
Pregnancy
Rats
Rats, Sprague-Dawley
Recombinant Proteins / pharmacology,  therapeutic use*
Vascular Endothelial Growth Factor A / pharmacology,  therapeutic use*
Vascular Endothelial Growth Factor Receptor-2 / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Recombinant Proteins; 0/Vascular Endothelial Growth Factor A; 0/vascular endothelial growth factor A, rat; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-2

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