| First Author | Tzima E | Year | 2005 |
| Journal | Nature | Volume | 437 |
| Issue | 7057 | Pages | 426-31 |
| PubMed ID | 16163360 | Mgi Jnum | J:101492 |
| Mgi Id | MGI:3604164 | Doi | 10.1038/nature03952 |
| Citation | Tzima E, et al. (2005) A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437(7057):426-31 |
| abstractText | 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. |
