title: Vasculogenesis, angiogenesis and the molecular organisation of endothelial junctions in the early human placenta.
abstract: Vasculogenesis and angiogenesis are regulated by the capacity of endothelial cells to adhere to each other and form new tubes. The presence and role of junctional adhesion molecules during physiological vasculogenesis is unknown. Using ultrastructural and immunocytochemical approaches, we compared the junctional phenotype of developing vessels of the first-trimester human placenta with vessels in the last trimester; the latter include newly formed terminal capillaries and the quiescent vascular bed. First-trimester placental vessels contained the adherens junctional molecules, vascular endothelial cadherin and alpha- and beta-catenin but lacked plakoglobin, the component of fully differentiated adherens junctions. Furthermore, these vessels did not contain the transmembrane tight junctional molecules occludin and claudin-1 and -2. This profile reflects the phenotype of terminal capillaries but differs from large vessels of the full-term placenta. Electron microscopic studies revealed that endothelial tight junctions are present in the first-trimester placenta. Thus, occludin and claudin-1 appear to play no part in the formation of endothelial tight junctions, but are a later requirement. In the early placenta, the predominant growth factor appears to be vascular endothelial growth factor (VEGF), whilst at term, angiopoietin-1 was present in large vessels, with intense angiopoietin-2 immunofluorescence (and VEGF) located in terminal villous capillaries. Thus, endothelial junctions in the human placenta possess two distinct molecular phenotypes, i.e. stable or dynamic, dependent on maturity and plasticity. These distinct phenotypes may be influenced by the angiopoietins/VEGF present in the placenta.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Queens Medical Centre, UK. Lopa.Leach@nottingham.ac.uk
authors.forename: Lopa
authors.initials: L
authors.lastname: Leach
authors.forename: Michael O
authors.initials: MO
authors.lastname: Babawale
authors.forename: Mark
authors.initials: M
authors.lastname: Anderson
authors.forename: Michael
authors.initials: M
authors.lastname: Lammiman
mesh_terms: D042683:Angiopoietin-1; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000032:analysis; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism / Q000502:physiology*; D008222:Lymphokines / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010920:Placenta / Q000098:blood supply* / Q000648:ultrastructure; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011247:Pregnancy; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis; D040262:Receptors, Vascular Endothelial Growth Factor; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051178:alpha Catenin; D051176:beta Catenin; D000099152:Cadherin 5
chemical_list: D042683:Angiopoietin-1; D015703:Antigens, CD; D015820:Cadherins; D003598:Cytoskeletal Proteins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D020794:Receptor Protein-Tyrosine Kinases; D017978:Receptors, Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051178:alpha Catenin; D051176:beta Catenin; D000099152:Cadherin 5; C467630:ANGPT1 protein, human; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human