TY - JOUR
T1 - Endothelial basement membrane laminin 511 is essential for shear stress response
AU - Di Russo, Jacopo
AU - Luik, Anna-Liisa
AU - Yousif, Lema
AU - Budny, Sigmund
AU - Oberleithner, Hans
AU - Hofschröer, Verena
AU - Klingauf, Juergen
AU - van Bavel, Ed
AU - Bakker, Erik Ntp
AU - Hellstrand, Per
AU - Bhattachariya, Anirban
AU - Albinsson, Sebastian
AU - Pincet, Frederic
AU - Hallmann, Rupert
AU - Sorokin, Lydia M.
PY - 2017
Y1 - 2017
N2 - 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
AB - 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
U2 - https://doi.org/10.15252/embj.201694756
DO - https://doi.org/10.15252/embj.201694756
M3 - Article
C2 - 27940654
SN - 0261-4189
VL - 36
SP - 183
EP - 201
JO - EMBO Journal
JF - EMBO Journal
IS - 2
ER -