Tie-2 and angiopoietin-2 expression at the fetal-maternal interface: a receptor ligand model for vascular remodelling.
The blood vessels at the fetal-maternal interface widen dramatically during pregnancy in order to increase blood flow to nourish the developing fetus. This vessel remodelling destroys normal vessel integrity and encompasses the dissolution of vessel muscle and elastic tissue. It also includes the displacement of endothelial cells by fetal trophoblasts that invade the maternal arteries of the uterus. Interaction between the endothelial cell receptor, Tie-2, and its recently discovered antagonist ligand, angiopoietin-2 (Ang-2), has been implicated in the loosening of vessel structure. Using Northern blot hybridization and RNA in-situ hybridization analysis the expression pattern of Tie-2, and Ang-2 in the placenta throughout pregnancy, was investigated. We found Ang-2 expressed in the syncytiotrophoblast during the first trimester. In addition to the expected expression of the Tie-2 receptor in both fetal and maternal endothelial cells, we observed Tie-2 expression in endovascular invasive trophoblasts. These cells of epithelial origin invade the uterine spiral arteries and acquire endothelial cell properties. The temporal- and lineage-specific pattern of expression of Tie-2 and Ang-2 suggests that this receptor-ligand pair functions during the critical phase of development of the fetal vasculature and reworking of the maternal vessels during normal placentation.
Goldman-Wohl
D S
DS
Department of Obstetrics and Gynecology, Hadassah-University Hospital, Mt Scopus, POB 24035, Jerusalem 91240, Israel.
Ariel
I
I
Greenfield
C
C
Lavy
Y
Y
Yagel
S
S
D042702:Angiopoietin-2; D015152:Blotting, Northern; D005260:Female; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D010920:Placenta / Q000098:blood supply / Q000378:metabolism*; D011247:Pregnancy; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D042787:Receptor, TIE-2; D014327:Trophoblasts / Q000378:metabolism; D014407:Tumor Cells, Cultured
D042702:Angiopoietin-2; D008024:Ligands; D011506:Proteins; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2