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

Bergmann, Astrid and Ahmad, Shakil and Cudmore, Melissa and Gruber, Achim D. and Wittschen, Petra and Lindenmaier, Werner and Christofori, Gerhard and Gross, Volkmar and Gonzalves, Andrey Ch da Costa and Gröne, Hermann-Josef and Ahmed, Asif and Weich, Herbert A.. (2010) Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model. Journal of cellular and molecular medicine, Vol. 14, H. 6B. S. 1857-1867.

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Official URL: http://edoc.unibas.ch/dok/A6005310

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Tumor Biology (Christofori)
UniBasel Contributors:Christofori, Gerhard M.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Dec 2012 13:03
Deposited On:07 Dec 2012 13:00

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