Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia

Z Li, Y Zhang, J Ying Ma, AM Kapoun, Q Shao… - …, 2007 - Am Heart Assoc
Z Li, Y Zhang, J Ying Ma, AM Kapoun, Q Shao, I Kerr, A Lam, G O'Young, F Sannajust…
Hypertension, 2007Am Heart Assoc
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 …
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.
Am Heart Assoc