Effect of Recombinant Placental Growth Factor 2 on Hypertension Induced by Full-Length Mouse Soluble fms-Like Tyrosine Kinase 1 Adenoviral Vector in Pregnant Mice
- 1 November 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 54 (5), 1129-1135
- https://doi.org/10.1161/hypertensionaha.109.134668
Abstract
The first aim of our study was to develop a pregnant mouse model for preeclampsia using adenoviral vector containing mouse full-length soluble fms-like tyrosine kinase 1 (sFlt-1) but not truncated sFlt-1. The second aim was to evaluate effects of recombinant mouse (rm) vascular endothelial growth factor (VEGF) and rm placental growth factor (PlGF) on a preeclampsia model induced by adenoviral vector containing mouse full-length sFlt-1. We injected adenoviral vector containing mouse full-length sFlt-1 on day 8.5 or 9.5 of gestation into pregnant Institute of Cancer Research mice, resulting in hypertension, proteinuria, and similar glomerular histological changes as those seen in human preeclamptic women with glomerular endotheliosis on day 16.5 or 17.5 of gestation. The preeclampsia models were treated with 100 μg/kg of rmVEGF164 (n=5), 100 μg/kg of rmPlGF-2 (n=5), or vehicle (n=7) twice a day for 2 days IP. The rmVEGF164 treatment significantly decreased the mean blood pressure on day 16.5 or 17.5 of gestation compared with the vehicle treatment (85±4 versus 97±2 mm Hg; P =0.018). The rmPlGF-2 treatment also significantly decreased the mean blood pressure on day 16.5 or 17.5 of gestation compared with the vehicle treatment (86±3 versus 97±2 mm Hg; P =0.018). However, proteinuria was not affected by either rmVEGF164 or rmPlGF-2. In conclusion, we, for the first time, created a mouse preeclampsia model using mouse full-length sFlt-1. VEGF and PlGF may be promising for ameliorating hypertension in women with preeclampsia. Additional study of PlGF as a potential drug for preeclampsia is warranted.Keywords
This publication has 34 references indexed in Scilit:
- Oxidative Stress Contributes to Soluble Fms-Like Tyrosine Kinase-1 Induced Vascular Dysfunction in Pregnant RatsAmerican Journal of Hypertension, 2009
- Nitric Oxide Formation Is Inversely Related to Serum Levels of Antiangiogenic Factors Soluble Fms-Like Tyrosine Kinase-1 and Soluble Endogline in PreeclampsiaHypertension, 2008
- Placental growth factor is a potent vasodilator of rat and human resistance arteriesAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- Cardiotoxicity associated with tyrosine kinase inhibitor sunitinibThe Lancet, 2007
- Recombinant Vascular Endothelial Growth Factor 121 Attenuates Hypertension and Improves Kidney Damage in a Rat Model of PreeclampsiaHypertension, 2007
- Sorafenib in Advanced Clear-Cell Renal-Cell CarcinomaNew England Journal of Medicine, 2007
- Soluble Endoglin and Other Circulating Antiangiogenic Factors in PreeclampsiaNew England Journal of Medicine, 2006
- Circulating Angiogenic Factors and the Risk of PreeclampsiaNew England Journal of Medicine, 2004
- Soluble Flt-1 (Soluble VEGFR-1), a Potent Natural Antiangiogenic Molecule in Mammals, Is Phylogenetically Conserved in AviansBiochemical and Biophysical Research Communications, 2002
- Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor.Proceedings of the National Academy of Sciences, 1993