title: Endothelial cell senescence is associated with disrupted cell-cell junctions and increased monolayer permeability.
abstract: BACKGROUND
  Cellular senescence is associated with cellular dysfunction and has been shown to occur in vivo in age-related cardiovascular diseases such as atherosclerosis. Atherogenesis is accompanied by intimal accumulation of LDL and increased extravasation of monocytes towards accumulated and oxidized LDL, suggesting an affected barrier function of vascular endothelial cells. Our objective was to study the effect of cellular senescence on the barrier function of non-senescent endothelial cells.
  
  
  METHODS
  Human umbilical vein endothelial cells were cultured until senescence. Senescent cells were compared with non-senescent cells and with co-cultures of non-senescent and senescent cells. Adherens junctions and tight junctions were studied. To assess the barrier function of various monolayers, assays to measure permeability for Lucifer Yellow (LY) and horseradish peroxidase (PO) were performed.
  
  
  RESULTS
  The barrier function of monolayers comprising of senescent cells was compromised and coincided with a change in the distribution of junction proteins and a down-regulation of occludin and claudin-5 expression. Furthermore, a decreased expression of occludin and claudin-5 was observed in co-cultures of non-senescent and senescent cells, not only between senescent cells but also along the entire periphery of non-senescent cells lining a senescent cell.
  
  
  CONCLUSIONS
  Our findings show that the presence of senescent endothelial cells in a non-senescent monolayer disrupts tight junction morphology of surrounding young cells and increases the permeability of the monolayer for LY and PO.
authors.affiliation: Department of Biomolecular Imaging, Faculty of Science, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands. j.a.post@uu.nl.
authors.forename: Vincent J D
authors.initials: VJ
authors.lastname: Krouwer
authors.forename: Liesbeth H P
authors.initials: LH
authors.lastname: Hekking
authors.forename: Miriam
authors.initials: M
authors.lastname: Langelaar-Makkinje
authors.forename: Elsa
authors.initials: E
authors.lastname: Regan-Klapisz
authors.forename: Jan Andries
authors.initials: JA
authors.lastname: Post