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) 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.
Li
Zhihe
Z
Scios Inc., Fremont, CA, USA.
Zhang
Ying
Y
Ying Ma
Jing
J
Kapoun
Ann M
AM
Shao
Qiming
Q
Kerr
Irene
I
Lam
Andrew
A
O'Young
Gilbert
G
Sannajust
Frederick
F
Stathis
Peter
P
Schreiner
George
G
Karumanchi
S Ananth
SA
Protter
Andrew A
AA
Pollitt
N Stephen
NS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D011225:Pre-Eclampsia / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D040301:Vascular Endothelial Growth Factor Receptor-2