Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Hemodynamic shear stress is a fundamental determinant of vascular remodeling and atherogenesis. Changes in focal adhesions, cytoskeletal organization and gene expression are major responses of endothelial cells to shear stress. Here, we show that activation of the small GTPase Rac is essential for gene expression and for providing spatial information for shear stress-induced cell alignment. Fluorescence resonance energy transfer (FRET) localizes activated Rac1 in the direction of flow. This directional Rac1 activation is downstream of shear-induced new integrin binding to extracellular matrix. Additionally, Rac1 mediates flow-induced stimulation of nuclear factor kappaB (NF-kappaB) and the subsequent expression of intercellular cell adhesion molecule 1 (ICAM-1), an adhesion receptor involved in the recruitment of leukocytes to atherosclerotic plaque. These studies provide a unifying model linking three of the main responses to shear stress that mediate both normal adaptation to hemodynamic forces and inflammatory dysfunction of endothelial cells in atherosclerosis.

Original publication

DOI

10.1093/emboj/cdf688

Type

Journal article

Journal

EMBO J

Publication Date

16/12/2002

Volume

21

Pages

6791 - 6800

Keywords

Animals, Cattle, Cell Adhesion, Cells, Cultured, Cytoskeleton, Dimerization, Energy Transfer, Enzyme Activation, GTP Phosphohydrolases, Gene Expression Regulation, Genes, Dominant, Green Fluorescent Proteins, Intercellular Adhesion Molecule-1, Leukocytes, Luciferases, Luminescent Proteins, Microscopy, Fluorescence, NF-kappa B, Plasmids, Protein Transport, Spectrometry, Fluorescence, Stress, Mechanical, Time Factors, Transfection, rac GTP-Binding Proteins, rac1 GTP-Binding Protein