Item Type: | Article |
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Title: | Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model |
Creators Name: | Bergmann, A., Ahmad, S., Cudmore, M., Gruber, A.D., Wittschen, P., Lindenmaier, W., Christofori, G., Gross, V., da Costa Gonzalves, A.C., Groene, H.J., 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 |
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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