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(Hypertension. 2007;50:686.)
© 2007 American Heart Association, Inc.

Original Articles

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

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

From Scios Inc. (Z.L., Y.Z., J.Y.M., A.M.K., Q.S., I.K., A.L., G.O., F.S., P.S., G.S., A.A.P., N.S.P.), Fremont, Calif; and Beth Israel Deaconess Medical Center (S.A.K.), Harvard Medical School, Boston, Mass.

Correspondence to N. Stephen Pollitt, 1037 Campbell Ave, Los Altos, CA 94024. E-mail steve{at}pollitts.net

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.

Key Words: VEGF121 • preeclampsia • sFlt-1 • blood pressure • glomerular endotheliosis • sVEGFR-1

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