title: Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia.
abstract: 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.affiliation: Scios Inc., Fremont, CA, USA.
authors.forename: Zhihe
authors.initials: Z
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Ying Ma
authors.forename: Ann M
authors.initials: AM
authors.lastname: Kapoun
authors.forename: Qiming
authors.initials: Q
authors.lastname: Shao
authors.forename: Irene
authors.initials: I
authors.lastname: Kerr
authors.forename: Andrew
authors.initials: A
authors.lastname: Lam
authors.forename: Gilbert
authors.initials: G
authors.lastname: O'Young
authors.forename: Frederick
authors.initials: F
authors.lastname: Sannajust
authors.forename: Peter
authors.initials: P
authors.lastname: Stathis
authors.forename: George
authors.initials: G
authors.lastname: Schreiner
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Protter
authors.forename: N Stephen
authors.initials: NS
authors.lastname: Pollitt
mesh_terms: 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
chemical_list: D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D040301:Vascular Endothelial Growth Factor Receptor-2