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
Naturejournal_title
Natureauthors
Tzima E,Irani-Tehrani M,Kiosses WB,Dejana E,Schultz DA,Engelhardt B,Cao G,DeLisser H,Schwartz MAdoi
10.1038/nature03952keywords:
subject
Has Abstractpub_date
2005-09-15 00:00:00pages
426-31issue
7057eissn
0028-0836issn
1476-4687pii
nature03952journal_volume
437pub_type
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