The phenotype of the human materno-fetal endothelial barrier: molecular occupancy of paracellular junctions dictate permeability and angiogenic plasticity.
In vitro models predict that molecular occupancy of endothelial junctions may regulate both barrier function and angiogenesis. Whether this is true in human vascular beds undergoing physiological angiogenesis has not been shown. This review presents data which demonstrate there are two distinct junctional phenotypes, 'activated' and 'stable', present in the vascular tree of the human placenta taken from two distinct highly angiogenic gestational periods (first and last trimester). Stability is conferred by the presence of occludin in tight junctions and plakoglobin in adherens junctions. Their localization may be influenced by vascular endothelial growth factor and angiopoietins 1 and 2 that have a similar temporal and site-specific differential expression. The junctional phenotypes are reversible, as shown in studies with endothelial cells isolated from placental microvessels and grown in the presence/absence of cAMP-enhancing agents. Reductions in protein levels and loss of junctional localization of adhesion molecules result in increased permeability to macromolecules, whilst up-regulation and re-targeting of these molecules inhibit cell proliferation and increase transendothelial resistance. These studies suggest junctional adhesion molecules can regulate physiological angiogenesis and vascular re-modelling. Moreover, the activated junctional phenotype of placental microvessels allows them to participate in increased growth and proliferation. This junctional immaturity appears to be at the expense of barrier function resulting in sites of maximal materno-fetal solute exchange.
Leach
Lopa
L
School of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, UK. lopa.leach@nottingham.ac.uk
D022005:Adherens Junctions; D002199:Capillary Permeability / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051180:Desmoplakins; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D018919:Neovascularization, Physiologic; D062793:Occludin; D021041:Placental Circulation / Q000502:physiology*; D011247:Pregnancy; D019108:Tight Junctions / Q000378:metabolism; D051185:gamma Catenin
D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D051185:gamma Catenin