Publikationsdatenbank

Reduction of Circulating Soluble Flt-1 Alleviates Preeclampsia-like Symptoms in a Mouse Model (2009)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Bergmann, Astrid

Ahmad, Shakil

Cudmore, Melissa

Gruber, Achim D.

Wittschen, Petra

Lindenmaier, Werner

Christofori, Gerhard

Gross, Volkmar

Costa Gonzalves, Andrey Ch. da

Gröne, Hermann-Josef

Ahmed, Asif

Weich, Herbert A.

Quelle

Journal of cellular and molecular medicine; 14(6) — S. 1857–1867

ISSN: 1582-4934

Sprache

Englisch

Verweise

DOI: 10.1111/j.1582-4934.2009.00820.x

Pubmed: 19538465

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
Gebäude 12
14163 Berlin
+49 30 838 62450

Abstract / Zusammenfassung

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.