Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1038/nature03952

Type

Journal article

Journal

Nature

Publication Date

15/09/2005

Volume

437

Pages

426 - 431

Keywords

Animals, Antigens, CD, Cadherins, Cattle, Cell Adhesion, Cells, Cultured, Endothelial Cells, Female, Gene Deletion, Mechanotransduction, Cellular, Mice, Mice, Knockout, Multiprotein Complexes, NF-kappa B, Platelet Endothelial Cell Adhesion Molecule-1, Rats, Stress, Mechanical, Vascular Endothelial Growth Factor Receptor-2