Placental-Specific sFLT-1 e15a Protein Is Increased in Preeclampsia, Antagonizes Vascular Endothelial Growth Factor Signaling, and Has Antiangiogenic Activity
| العنوان: | Placental-Specific sFLT-1 e15a Protein Is Increased in Preeclampsia, Antagonizes Vascular Endothelial Growth Factor Signaling, and Has Antiangiogenic Activity |
|---|---|
| المؤلفون: | Natalie K Binder, Alexis Shub, Louie Ye, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Roxanne Hastie, Ping Cannon, Kirsten R Palmer, Natalie J. Hannan, Laura Tuohey, Terrance Grant Johns |
| المصدر: | Hypertension. 66:1251-1259 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Adult, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Placenta, Blotting, Western, Angiogenesis Inhibitors, Biology, Preeclampsia, chemistry.chemical_compound, Pre-Eclampsia, Cell Movement, Pregnancy, Internal medicine, Human Umbilical Vein Endothelial Cells, Internal Medicine, medicine, Animals, Humans, Protein Isoforms, Endothelial dysfunction, Cells, Cultured, Vascular Endothelial Growth Factor Receptor-1, Reverse Transcriptase Polymerase Chain Reaction, Infant, Newborn, Kinase insert domain receptor, medicine.disease, Trophoblasts, Mice, Inbred C57BL, Vascular endothelial growth factor B, Endothelial stem cell, Vascular endothelial growth factor, Vascular endothelial growth factor A, Endocrinology, Microscopy, Fluorescence, Vascular endothelial growth factor C, chemistry, embryonic structures, Female, RNA Interference, Signal Transduction |
| الوصف: | In preeclampsia, the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFLT-1) is released from placenta into the maternal circulation, causing endothelial dysfunction and organ injury. A recently described splice variant, sFLT-1 e15a, is primate specific and the most abundant placentally derived sFLT-1. Therefore, it may be the major sFLT-1 isoform contributing to the pathophysiology of preeclampsia. sFLT-1 e15a protein remains poorly characterized: its bioactivity has not been comprehensively examined, and serum levels in normal and preeclamptic pregnancy have not been reported. We generated and validated an sFLT-1 e15a–specific ELISA to further characterize serum levels during pregnancy, and in the presence of preeclampsia. Furthermore, we performed assays to examine the bioactivity and antiangiogenic properties of sFLT-1 e15a protein. sFLT-1 e15a was expressed in the syncytiotrophoblast, and serum levels rose across pregnancy. Strikingly, serum levels were increased 10-fold in preterm preeclampsia compared with normotensive controls. We confirmed sFLT-1 e15a is bioactive and is able to inhibit vascular endothelial growth factor signaling of vascular endothelial growth factor receptor 2 and block downstream Akt phosphorylation. Furthermore, sFLT-1 e15a has antiangiogenic properties. sFLT-1 e15a decreased endothelial cell migration, invasion, and inhibited endothelial cell tube formation. Administering sFLT-1 e15a blocked vascular endothelial growth factor induced sprouts from mouse aortic rings ex vivo. We have demonstrated that sFLT-1 e15a is increased in preeclampsia, antagonizes vascular endothelial growth factor signaling, and has antiangiogenic activity. Future development of diagnostics and therapeutics for preeclampsia should consider targeting placentally derived sFLT-1 e15a. |
| تدمد: | 1524-4563 0194-911X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::807264e44b2b41a2189bd972217e624e https://doi.org/10.1161/hypertensionaha.115.05883 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....807264e44b2b41a2189bd972217e624e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244563 0194911X |
|---|