Recombinant Vascular Endothelial Growth Factor 121 Attenuates Hypertension and Improves Kidney Damage in a Rat Model of Preeclampsia

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) r...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2007-10, Vol.50 (4), p.686-692
Main Authors: Li, Zhihe, Zhang, Ying, Ma, Jing Ying, Kapoun, Ann M, Shao, Qiming, Kerr, Irene, Lam, Andrew, O’Young, Gilbert, Sannajust, Frederick, Stathis, Peter, Schreiner, George, Karumanchi, S Ananth, Protter, Andrew A, Pollitt, N Stephen
Format: Article
Language:English
Subjects:
Animals
Arterial hypertension. Arterial hypotension
Biological and medical sciences
Blood and lymphatic vessels
Blood Pressure - drug effects
Cardiology. Vascular system
Clinical manifestations. Epidemiology. Investigative techniques. Etiology
Disease Models, Animal
Dose-Response Relationship, Drug
Experimental diseases
Female
Gene Expression Regulation - drug effects
Hypertension - drug therapy
Hypertension - physiopathology
Kidney - drug effects
Kidney - metabolism
Kidney - pathology
Medical sciences
Pre-Eclampsia - drug therapy
Pre-Eclampsia - physiopathology
Pregnancy
Rats
Rats, Sprague-Dawley
Recombinant Proteins - pharmacology
Recombinant Proteins - therapeutic use
Vascular Endothelial Growth Factor A - pharmacology
Vascular Endothelial Growth Factor A - therapeutic use
Vascular Endothelial Growth Factor Receptor-2 - genetics
Vascular Endothelial Growth Factor Receptor-2 - metabolism
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Summary: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 μg/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.
ISSN:0194-911X
1524-4563
DOI:10.1161/HYPERTENSIONAHA.107.092098