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

Abstract:

:Shear stress is a fundamental determinant of vascular homeostasis, regulating vascular remodelling, cardiac development and atherogenesis, 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 expression. 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-kappaB and downstream inflammatory genes in regions of disturbed flow. Therefore, this mechanosensing pathway is required for the earliest-known events in atherogenesis.

journal_name

Nature

journal_title

Nature

authors

Tzima E,Irani-Tehrani M,Kiosses WB,Dejana E,Schultz DA,Engelhardt B,Cao G,DeLisser H,Schwartz MA

doi

10.1038/nature03952

keywords:

subject

Has Abstract

pub_date

2005-09-15 00:00:00

pages

426-31

issue

7057

eissn

0028-0836

issn

1476-4687

pii

nature03952

journal_volume

437

pub_type

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