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Herr, F; Liang, OD; Herrero, J; Lang, U; Preissner, KT; Han, VK; Zygmunt, M.
Possible angiogenic roles of insulin-like growth factor II and its receptors in uterine vascular adaptation to pregnancy.
J CLIN ENDOCRINOL METAB 2003 88: 4811-4817. Doi: 10.1210/jc.2003-030243 [OPEN ACCESS]
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Lang Uwe
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Abstract:
Adaptation of the maternal uterine vasculature is essential for normal fetal and placental development in which angiogenesis is considered one of the most critical adaptive changes during pregnancy. Highly expressed in cytotrophoblasts and maternal endothelial cells during pregnancy, IGF-II promotes cell migration and regulates fetal and placental growth. We hypothesized that IGF-II regulates uterine angiogenesis during pregnancy. Both uterine vasculature and isolated uterine microvascular endothelial cells expressed high levels of IGF-II and IGF-II/mannose-6 phosphate receptor mRNA as shown by in situ hybridization. Physiological concentrations of IGF-II significantly increased vessel formation, as shown by a three-dimensional angiogenesis assay in vitro or a chicken chorionallantoic membrane assay in vivo. The angiogenic response of IGF-II could be reversed by the addition of beta-galactosidase or rabbit-antihuman IGF-II/M6P receptor antiserum, whereas blocking antibodies against IGF-I receptor or insulin receptor influenced IGF-II-induced sprout formation. IGF-II promoted migration of endothelial cells (10-250 ng/ml) tested in a modified Boyden chamber, but no stimulating effect on proliferation was observed. The application of several intracellular signal transduction molecules and their inhibitors indicated that protein kinase C and G(i) protein might play a role in the IGF-II-induced angiogenesis. Our results suggest an important angiogenic role of IGF-II in the vascular adaptation to pregnancy.
Find related publications in this database (using NLM MeSH Indexing)
Adaptation, Physiological - physiology
Animals - physiology
Cell Division - drug effects
Cell Line - drug effects
Cell Movement - drug effects
Chick Embryo - drug effects
Cross-Linking Reagents - metabolism
Endothelium, Vascular - cytology
Female - cytology
Gene Expression - physiology
Humans - physiology
Insulin-Like Growth Factor II - genetics
Iodine Radioisotopes - diagnostic use
Neovascularization, Physiologic - drug effects
Pregnancy - drug effects
RNA, Messenger - analysis
Receptor, IGF Type 2 - genetics
Umbilical Veins - cytology
Uterus - blood supply

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