A mechanosensory complex that mediates the endothelial cell response to fluid shear stress

Eleni Tzima, Mohamed Irani-Tehrani, William B. Kiosses, Elizabetta Dejana, David A. Schultz, Britta Engelhardt, Gaoyuan Cao, Horace DeLisser and Martin Alexander Schwartz ()
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Eleni Tzima: The Scripps Research Institute
Mohamed Irani-Tehrani: The Scripps Research Institute
William B. Kiosses: The Scripps Research Institute
Elizabetta Dejana: University of Milan
David A. Schultz: University of California at San Diego
Britta Engelhardt: University of Bern
Gaoyuan Cao: University of Pennsylvania Medical Center
Horace DeLisser: University of Pennsylvania Medical Center
Martin Alexander Schwartz: The Scripps Research Institute

Nature, 2005, vol. 437, issue 7057, 426-431

Abstract: Abstract Shear stress is a fundamental determinant of vascular homeostasis, regulating vascular remodelling, cardiac development and atherogenesis1, but the mechanisms of transduction are poorly understood. Previous work showed that the conversion of integrins to a high-affinity state mediates a subset of shear responses, including cell alignment and gene expression2,3,4. Here we investigate the pathway upstream of integrin activation. PECAM-1 (which directly transmits mechanical force), vascular endothelial cell cadherin (which functions as an adaptor) and VEGFR2 (which activates phosphatidylinositol-3-OH kinase) comprise a mechanosensory complex. Together, these receptors are sufficient to confer responsiveness to flow in heterologous cells. In support of the relevance of this pathway in vivo, PECAM-1-knockout mice do not activate NF-κB and downstream inflammatory genes in regions of disturbed flow. Therefore, this mechanosensing pathway is required for the earliest-known events in atherogenesis.

Date: 2005
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DOI: 10.1038/nature03952

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