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Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model

Item Type:Article
Title:Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model
Creators Name:Bergmann, A. and Ahmad, S. and Cudmore, M. and Gruber, A.D. and Wittschen, P. and Lindenmaier, W. and Christofori, G. and Gross, V. and da Costa Gonzalves, A.C. and Groene, H.J. and Ahmed, A. and Weich, H.A.
Abstract:Preeclampsia (PE) is characterized by widespread endothelial damage with hypertension, proteinuria, glomeruloendotheliosis and elevated soluble Flt-1 (sFlt-1), a natural occurring antagonist of vascular endothelial growth factor (VEGF). Cancer patients receiving anti-VEGF therapy exhibit similar symptoms. We suggested that a decrease in circulating sFlt-1 would alleviate the symptoms associated with PE. Adenoviral (Adv) overexpression of sFlt-1 induced proteinuria, caused glomerular damage and increase in blood pressure in female Balb/c mice. Circulating level of sFlt-1 above 50 ng/ml plasma induced severe vascular damage and glomerular endotheliosis. Albumin concentration in urine was elevated up to 30-fold, compared to control AdvGFP-treated animals. The threshold of kidney damage was in the range of 20-30 ng/ml sFlt-1 in plasma (8-15 ng/ml in urine). Co-administration of AdvsFlt-1 with AdvVEGF to neutralize circulating sFlt-1 resulted in more than a 70% reduction in free sFlt-1 in plasma, more than 80% reduction in urine and rescued the damaging effect of sFlt-1 on the kidneys. This demonstrates that below a critical threshold sFlt-1 fails to elicit damage to the fenestrated endothelium and that co-expression of VEGF is able to rescue effects mediated by sFlt-1 overexpression.
Keywords:Preeclampsia, Vascular Endothelial Growth Factor, fms-Like Tyrosine Kinase Receptor, Vascular Disease, Animals, Mice
Source:Journal of Cellular and Molecular Medicine
ISSN:1582-1838
Publisher:Carol Davila University Press (Romania)
Volume:14
Number:6B
Page Range:1857-1867
Date:June 2010
Official Publication:https://doi.org/10.1111/j.1582-4934.2009.00820.x
PubMed:View item in PubMed

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