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Endothelial basement membrane laminin 511 is essential for shear stress response

Di Russo, Jacopo; Luik, Anna Liisa; Yousif, Lema; Budny, Sigmund; Oberleithner, Hans; Hofschröer, Verena; Klingauf, Juergen; van Bavel, Ed; Bakker, Erik N T P and Hellstrand, Per LU , et al. (2017) In EMBO Journal 36(2). p.183-201
Abstract

Shear detection and mechanotransduction by arterial endothelium requires junctional complexes containing PECAM-1 and VE-cadherin, as well as firm anchorage to the underlying basement membrane. While considerable information is available for junctional complexes in these processes, gained largely from in vitro studies, little is known about the contribution of the endothelial basement membrane. Using resistance artery explants, we show that the integral endothelial basement membrane component, laminin 511 (laminin α5), is central to shear detection and mechanotransduction and its elimination at this site results in ablation of dilation in response to increased shear stress. Loss of endothelial laminin 511 correlates with reduced cortical... (More)

Shear detection and mechanotransduction by arterial endothelium requires junctional complexes containing PECAM-1 and VE-cadherin, as well as firm anchorage to the underlying basement membrane. While considerable information is available for junctional complexes in these processes, gained largely from in vitro studies, little is known about the contribution of the endothelial basement membrane. Using resistance artery explants, we show that the integral endothelial basement membrane component, laminin 511 (laminin α5), is central to shear detection and mechanotransduction and its elimination at this site results in ablation of dilation in response to increased shear stress. Loss of endothelial laminin 511 correlates with reduced cortical stiffness of arterial endothelium in vivo, smaller integrin β1-positive/vinculin-positive focal adhesions, and reduced junctional association of actin–myosin II. In vitro assays reveal that β1 integrin-mediated interaction with laminin 511 results in high strengths of adhesion, which promotes p120 catenin association with VE-cadherin, stabilizing it at cell junctions and increasing cell–cell adhesion strength. This highlights the importance of endothelial laminin 511 in shear response in the physiologically relevant context of resistance arteries.

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publication status
published
subject
keywords
endothelial cells, focal adhesions, laminin 511, shear stress, VE-cadherin
in
EMBO Journal
volume
36
issue
2
pages
19 pages
publisher
Oxford University Press
external identifiers
  • scopus:85006386904
  • wos:000393317800006
ISSN
0261-4189
DOI
10.15252/embj.201694756
language
English
LU publication?
yes
id
14c4c26f-f38d-491d-9121-d9efc589b460
date added to LUP
2017-03-03 09:52:31
date last changed
2018-01-07 11:53:54
@article{14c4c26f-f38d-491d-9121-d9efc589b460,
  abstract     = {<p>Shear detection and mechanotransduction by arterial endothelium requires junctional complexes containing PECAM-1 and VE-cadherin, as well as firm anchorage to the underlying basement membrane. While considerable information is available for junctional complexes in these processes, gained largely from in vitro studies, little is known about the contribution of the endothelial basement membrane. Using resistance artery explants, we show that the integral endothelial basement membrane component, laminin 511 (laminin α5), is central to shear detection and mechanotransduction and its elimination at this site results in ablation of dilation in response to increased shear stress. Loss of endothelial laminin 511 correlates with reduced cortical stiffness of arterial endothelium in vivo, smaller integrin β1-positive/vinculin-positive focal adhesions, and reduced junctional association of actin–myosin II. In vitro assays reveal that β1 integrin-mediated interaction with laminin 511 results in high strengths of adhesion, which promotes p120 catenin association with VE-cadherin, stabilizing it at cell junctions and increasing cell–cell adhesion strength. This highlights the importance of endothelial laminin 511 in shear response in the physiologically relevant context of resistance arteries.</p>},
  author       = {Di Russo, Jacopo and Luik, Anna Liisa and Yousif, Lema and Budny, Sigmund and Oberleithner, Hans and Hofschröer, Verena and Klingauf, Juergen and van Bavel, Ed and Bakker, Erik N T P and Hellstrand, Per and Bhattachariya, Anirban and Albinsson, Sebastian and Pincet, Frederic and Hallmann, Rupert and Sorokin, Lydia M.},
  issn         = {0261-4189},
  keyword      = {endothelial cells,focal adhesions,laminin 511,shear stress,VE-cadherin},
  language     = {eng},
  month        = {01},
  number       = {2},
  pages        = {183--201},
  publisher    = {Oxford University Press},
  series       = {EMBO Journal},
  title        = {Endothelial basement membrane laminin 511 is essential for shear stress response},
  url          = {http://dx.doi.org/10.15252/embj.201694756},
  volume       = {36},
  year         = {2017},
}