Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model
| العنوان: | Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model |
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| المؤلفون: | Herbert A. Weich, Melissa J. Cudmore, Gerhard Christofori, Volkmar Gross, Shakil Ahmad, Werner Lindenmaier, Asif Ahmed, Andrey Ch. da Costa Gonzalves, Astrid Bergmann, Hermann Josef Gröne, Achim D. Gruber, Petra Wittschen |
| المصدر: | Journal of Cellular and Molecular Medicine Bergmann, A, Ahmad, S, Cudmore, M, Gruber, A D, Wittschen, P, Lindenmaier, W, Christofori, G, Gross, V, Gonzalves, A C D C, Gröne, H-J, Ahmed, A & Weich, H A 2010, ' Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model ', Journal of Cellular and Molecular Medicine, vol. 14, no. 6B, pp. 1857-67 . https://doi.org/10.1111/j.1582-4934.2009.00820.x |
| بيانات النشر: | Wiley, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Vascular Endothelial Growth Factor A, Blood Pressure, 030204 cardiovascular system & hematology, Kidney, Mice, chemistry.chemical_compound, 0302 clinical medicine, Pre-Eclampsia, Heart Rate, Pregnancy, fms-like tyrosine kinase receptor, 0303 health sciences, Proteinuria, vascular endothelial growth factor, vascular disease, 3. Good health, Vascular endothelial growth factor, Vascular endothelial growth factor A, medicine.anatomical_structure, embryonic structures, Molecular Medicine, Female, medicine.symptom, Glomerular Filtration Rate, Protein Binding, medicine.medical_specialty, Endothelium, Renal function, Enzyme-Linked Immunosorbent Assay, Biology, Preeclampsia, preeclampsia, 03 medical and health sciences, Internal medicine, medicine, Animals, 030304 developmental biology, Vascular Endothelial Growth Factor Receptor-1, Albumin, Original Articles, Cell Biology, medicine.disease, Vascular Endothelial Growth Factor Receptor-2, Disease Models, Animal, Endocrinology, Solubility, chemistry |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1582-4934 1582-1838 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cfaf643c0288f0890ce9519c058d422e https://doi.org/10.1111/j.1582-4934.2009.00820.x |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....cfaf643c0288f0890ce9519c058d422e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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