In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 101, No. 7 ( 2007-09-28), p. 682-691
Abstract:
α 2 -adrenoceptors are essential presynaptic regulators of norepinephrine release from sympathetic nerves. Previous studies in mice with targeted deletions in the 3 α 2 -adrenoceptor genes have indicated that these receptors are essential for embryonic development. In the present study, we searched for the α 2 -adrenoceptor subtype(s) involved in placental development and its molecular mechanism using mice carrying targeted deletions in α 2 -adrenoceptor genes. Congenic α 2B -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 α 2B -deficient placentae. The type 1 receptor for vascular endothelial growth factor (Flt1), which is coexpressed with α 2B -adrenoceptors in spongiotrophoblast and giant cells of the placenta, was found to be 2.3-fold upregulated in α 2B -deficient placentae. Neutralization of Flt1 and its soluble splice variant sFlt1 by a specific antibody in vivo prevented the vascular defect in α 2B -deficient placentae at embryonic day 10.5. Thus, α 2B -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.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/CIRCRESAHA.107.151563
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2007
detail.hit.zdb_id:
1467838-X
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