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Publication : Intra-vessel heterogeneity establishes enhanced sites of macromolecular leakage downstream of laminin α5.

First Author  Richards M Year  2021
Journal  Cell Rep Volume  35
Issue  12 Pages  109268
PubMed ID  34161758 Mgi Jnum  J:306616
Mgi Id  MGI:6717176 Doi  10.1016/j.celrep.2021.109268
Citation  Richards M, et al. (2021) Intra-vessel heterogeneity establishes enhanced sites of macromolecular leakage downstream of laminin alpha5. Cell Rep 35(12):109268
abstractText  Endothelial cells display heterogeneous properties based on location and function. How this heterogeneity influences endothelial barrier stability both between and within vessel subtypes is unexplored. In this study, we find that endothelial cells exhibit heterogeneous barrier properties on inter-organ and intra-vessel levels. Using intravital microscopy and sequential stimulation of the ear dermis with vascular endothelial growth factor-A (VEGFA) and/or histamine, we observe distinct, reappearing sites, common for both agonists, where leakage preferentially takes place. Through repetitive stimulation of the diaphragm and trachea, we find inter-organ conservation of such predetermined leakage sites. Qualitatively, predetermined sites display distinct leakage properties and enhanced barrier breakdown compared to less susceptible regions. Mechanistically, laminin alpha5 is reduced at predetermined sites, which is linked to reduced junctional vascular endothelial (VE)-cadherin and enhanced VEGFA-induced VE-cadherin phosphorylation. These data highlight functional intra-vessel heterogeneity that defines predetermined sites with distinct leakage properties and that may disproportionately impact pathological vascular leakage.
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