doi: 10.1161/01.ATV.0000175755.93591.56
© 2005 American Heart Association, Inc.
Editorials |
Even Flow
Shear Cues Vascular Development
From the Carolina Cardiovascular Biology Center and Departments of Medicine, Pharmacology, and Cell and Developmental Biology, University of North Carolina, Chapel Hill.
Correspondence to Cam Patterson, MD, Director, Division of Cardiology and Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill, 8200 Medical Biomolecular Research Building, Chapel Hill, NC 27599-7126. E-mail cpatters@med.unc.edu
Key Words: endothelium • shear stress • development • stem cell
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The appreciation that biomechanical forces induce signaling responses that regulate vascular tone and inflammatory responses has had a paradigm-shifting effect on our understanding of vascular biology. Endothelial cells are constantly exposed to rheologically imposed forces that vary due to vascular anatomic features and hemodynamic parameters, and of course shear fluctuates cyclically during the cardiac cycle. Simple laminar flow and high shear forces elicit a cellular response characterized by quiescence and alignment of endothelial cells in the direction of fluid flow, whereas disturbed flow and low shear forces induce an inflammatory procoagulant phenotype. These cellular effects are mediated through well-defined signaling pathways and gene expression responses. The cellular sensors or receptors for shear forces are incompletely characterized, but detection of stress seems to depend on the transmission of forces to points of cell–matrix and cell–cell attachment and requires specific conformational activation of integrins.1 From a pathophysiological perspective, disturbed laminar flow has been linked to inflammatory responses that initiate atheroma formation and elicit plaque instability. It is also generally accepted that flow is required for some aspects of vascular remodeling during vascular development and in adult angiogenic responses; however, specific roles for flow in vascular developmental programs have been incompletely characterized.
See page 1817
Two recent reports, including one published in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology,2 illuminate a critical role for fluid shear stress in triggering specific early steps in developmental programs in the vascular endothelium. The studies by Chen and colleagues use C3H10T1/2 cells, which are a
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Arterioscler Thromb Vasc Biol 2005 25: 1817-1823.