%0 Journal Article %1 Muthig.2007 %A Muthig, V. %A Gilsbach, R. %A Haubold, M. %A Philipp, M. %A Ivacevic, T. %A Gessler, M. %A Hein, L. %D 2007 %J Circ Res %K Animals C57BL Endothelial Factor Female Growth Mice Mice;Inbred Mice;Knockout Neovascularization;Pathologic/*metabolism Placenta/*blood Pregnancy Receptor-1/*biosynthesis/genetics/physiology Receptors;Adrenergic;alpha-2/*deficiency/genetics/*metabolism Solubility Up-Regulation/*physiology Vascular supply/*metabolism %N 7 %P 682--691 %T Upregulation of soluble vascular endothelial growth factor receptor 1 contributes to angiogenesis defects in the placenta of alpha 2B-adrenoceptor deficient mice %V 101 %X Alpha2-adrenoceptors are essential presynaptic regulators of norepinephrine release from sympathetic nerves. Previous studies in mice with targeted deletions in the 3 alpha2-adrenoceptor genes have indicated that these receptors are essential for embryonic development. In the present study, we searched for the alpha2-adrenoceptor subtype(s) involved in placental development and its molecular mechanism using mice carrying targeted deletions in alpha2-adrenoceptor genes. Congenic alpha2B-adrenoceptor-deficient mice (Adra2b-/-) developed a defect in fetal and maternal vessel formation in the placenta labyrinth at embryonic day 10.5. This defect was accompanied by reduced endothelial cell proliferation and decreased extracellular signal-regulated kinase 1/2 phosphorylation levels in Adra2b-/- as compared with Adra2b+/+ placentae. Microarray analysis of wild-type and mutant placentae (maternal genotype Adra2b+/-) revealed 179 genes, which were significantly up- or downregulated >1.5-fold in alpha2B-deficient placentae. The type 1 receptor for vascular endothelial growth factor (Flt1), which is coexpressed with alpha2B-adrenoceptors in spongiotrophoblast and giant cells of the placenta, was found to be 2.3-fold upregulated in alpha2B-deficient placentae. Neutralization of Flt1 and its soluble splice variant sFlt1 by a specific antibody in vivo prevented the vascular defect in alpha2B-deficient placentae at embryonic day 10.5. Thus, alpha2B-adrenoceptors are essential to suppress antiangiogenic (s)Flt1 in spongiotrophoblasts to control the coordinated formation of a vascular labyrinth of fetal and maternal blood vessels in the murine placenta during development.

@article{Muthig.2007, abstract = {Alpha2-adrenoceptors are essential presynaptic regulators of norepinephrine release from sympathetic nerves. Previous studies in mice with targeted deletions in the 3 alpha2-adrenoceptor genes have indicated that these receptors are essential for embryonic development. In the present study, we searched for the alpha2-adrenoceptor subtype(s) involved in placental development and its molecular mechanism using mice carrying targeted deletions in alpha2-adrenoceptor genes. Congenic alpha2B-adrenoceptor-deficient mice (Adra2b-/-) developed a defect in fetal and maternal vessel formation in the placenta labyrinth at embryonic day 10.5. This defect was accompanied by reduced endothelial cell proliferation and decreased extracellular signal-regulated kinase 1/2 phosphorylation levels in Adra2b-/- as compared with Adra2b+/+ placentae. Microarray analysis of wild-type and mutant placentae (maternal genotype Adra2b+/-) revealed 179 genes, which were significantly up- or downregulated >1.5-fold in alpha2B-deficient placentae. The type 1 receptor for vascular endothelial growth factor (Flt1), which is coexpressed with alpha2B-adrenoceptors in spongiotrophoblast and giant cells of the placenta, was found to be 2.3-fold upregulated in alpha2B-deficient placentae. Neutralization of Flt1 and its soluble splice variant sFlt1 by a specific antibody in vivo prevented the vascular defect in alpha2B-deficient placentae at embryonic day 10.5. Thus, alpha2B-adrenoceptors are essential to suppress antiangiogenic (s)Flt1 in spongiotrophoblasts to control the coordinated formation of a vascular labyrinth of fetal and maternal blood vessels in the murine placenta during development.}, added-at = {2013-01-29T13:47:26.000+0100}, author = {Muthig, V. and Gilsbach, R. and Haubold, M. and Philipp, M. and Ivacevic, T. and Gessler, M. and Hein, L.}, biburl = {https://www.bibsonomy.org/bibtex/2ce1c018ce3b5cfc966115c1e66cbdad9/ebch}, interhash = {b2e89b8c9eb67d0952137159e38fa653}, intrahash = {ce1c018ce3b5cfc966115c1e66cbdad9}, journal = {Circ Res}, keywords = {Animals C57BL Endothelial Factor Female Growth Mice Mice;Inbred Mice;Knockout Neovascularization;Pathologic/*metabolism Placenta/*blood Pregnancy Receptor-1/*biosynthesis/genetics/physiology Receptors;Adrenergic;alpha-2/*deficiency/genetics/*metabolism Solubility Up-Regulation/*physiology Vascular supply/*metabolism}, number = 7, pages = {682--691}, timestamp = {2013-01-29T13:47:29.000+0100}, title = {Upregulation of soluble vascular endothelial growth factor receptor 1 contributes to angiogenesis defects in the placenta of alpha 2B-adrenoceptor deficient mice}, volume = 101, year = 2007 }