Endothelial basement membrane laminin 511 is essential for shear stress response |
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| Authors: | Jacopo Di Russo Anna‐Liisa Luik Lema Yousif Sigmund Budny Hans Oberleithner Verena Hofschröer Juergen Klingauf Ed van Bavel Erik NTP Bakker Per Hellstrand Anirban Bhattachariya Sebastian Albinsson Frederic Pincet Rupert Hallmann Lydia M Sorokin |
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| Institution: | 1. Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster, Germany;2. Cells‐in‐Motion Cluster of Excellence, University of Muenster, Muenster, Germany;3. Institute of Physiology II, University of Muenster, Muenster, Germany;4. Institute of Medical Physics, University of Muenster, Muenster, Germany;5. Biomedical Engineering and Physics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;6. Department of Experimental Medical Science, Lund University, Lund, Sweden;7. Laboratoire de Physique Statistique, école Normale Superieure – PSL Research University, Paris, France;8. CNRS UMR8550, Sorbonne Universités ? UPMC Univ Paris 06, Université Paris, Paris, France |
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| 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 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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| Keywords: | endothelial cells focal adhesions laminin 511 shear stress VE‐cadherin |
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