Adenoviral Delivery of VEGF 121 Early in Pregnancy Prevents Spontaneous Development of Preeclampsia in BPH/5 Mice
| Autor: | Ram V. Sharma, Christine J. Weydert, Ashley K. Woods, Scott D. Butler, Robin L. Davisson, Yi Zhou, Darren S. Hoffmann |
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| Rok vydání: | 2011 |
| Předmět: |
Vascular Endothelial Growth Factor A
Placental growth factor medicine.medical_specialty Angiogenesis Placenta Genetic Vectors Pregnancy Proteins urologic and male genital diseases Article Adenoviridae Preeclampsia Pathogenesis Mice chemistry.chemical_compound Pre-Eclampsia Pregnancy Internal medicine Internal Medicine Animals Medicine Placenta Growth Factor Fetus Vascular Endothelial Growth Factor Receptor-1 Proteinuria urogenital system business.industry Genetic Therapy medicine.disease Mice Inbred C57BL Vascular endothelial growth factor Vascular endothelial growth factor A Endocrinology chemistry Female medicine.symptom business |
| Zdroj: | Hypertension. 57:94-102 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.110.160242 |
| Popis: | An imbalance in circulating proangiogenic and antiangiogenic factors is postulated to play a causal role in preeclampsia (PE). We have described an inbred mouse strain, BPH/5, which spontaneously develops a PE-like syndrome including late-gestational hypertension, proteinuria, and poor feto-placental outcomes. Here we tested the hypothesis that an angiogenic imbalance during pregnancy in BPH/5 mice leads to the development of PE-like phenotypes in this model. Similar to clinical findings, plasma from pregnant BPH/5 showed reduced levels of free vascular endothelial growth factor (VEGF) and placental growth factor (PGF) compared to C57BL/6 controls. This was paralleled by a marked decrease in VEGF protein and Pgf mRNA in BPH/5 placentae. Surprisingly, antagonism by the soluble form of the FLT1 receptor (sFLT1) did not appear to be the cause of this reduction, as sFLT1 levels were unchanged or even reduced in BPH/5 compared to controls. Adenoviral-mediated delivery of VEGF 121 (Ad-VEGF) via tail vein at embryonic day 7.5 normalized both the plasma-free VEGF levels in BPH/5 and restored the in vitro angiogenic capacity of serum from these mice. Ad-VEGF also reduced the incidence of fetal resorptions and prevented the late-gestational spike in blood pressure and proteinuria observed in BPH/5. These data underscore the importance of dysregulation of angiogenic factors in the pathogenesis of PE and suggest the potential utility of early proangiogenic therapies in treating this disease. |
| Databáze: | OpenAIRE |
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