doi: 10.1161/01.RES.0000200162.94463.d7
© 2006 American Heart Association, Inc.
Review |
Role of Small GTPases in Endothelial Cytoskeletal Dynamics and the Shear Stress Response
From the Department of Cell and Molecular Physiology, Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill.
Correspondence to Dr Eleni Tzima, University of North Carolina, Chapel Hill, Department of Cell and Molecular Physiology, 6341C Medical Biomolecular Research Building, 103 Mason Farm Rd, CB7545, Chapel Hill, NC 27599. E-mail etzima{at}med.unc.edu
Guest Editor: This Review is part of a thematic series on The Role of Small GTPases in Cardiovascular Biology, which includes the following articles:
Rho GTPases, Statins, and Nitric Oxide
Role of Small GTPases in Endothelial Cytoskeletal Dynamics and the Sheer Stress Response
Rho Kinases in Cardiovascular Physiology and Pathophysiology
Regulation of NADPH Oxidases: The Role of Rac Proteins
Rho GTPases and Signaling by Endothelial Receptors
The Rac and Rho Hall of Fame: A Decade of Hypertrophic Signaling Hits
Anne Ridley
Fluid shear stress caused by blood flow is a major determinant of vascular remodeling and arterial tone and can lead to development of atherosclerosis. The endothelial monolayer in vivo acts as a signal transduction interface for hemodynamic forces; these forces determine the shape, cytoskeletal organization, and function of endothelial cells, allowing the vessels to cope with physiological or pathological conditions. The Ras superfamily of GTPases have been revealed to be master regulators of many cellular activities. In particular, the GTPases RhoA, Rac1, and Cdc42 are known to regulate cell shape changes through effects on the cytoskeleton, but their ability to influence polarity, microtubule dynamics, and transcription factor activity is just as significant. Shear stress modulates the activity of small GTPases, which are critical for both cytoskeletal reorganization and changes in gene expression in response to shear stress. The goal of this article is to review what is known about Ras and more so about Rho GTPases in mechanotransduction and the responses of cells to fluid flow. Several distinct signaling pathways can be coordinately activated by flow, and small GTPases are strongly implicated in some of them; thus possible connections will be explored and a unifying hypothesis offered.
Key Words: GTPases • shear stress • endothelium • cytoskeleton
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