doi: 10.1161/CIRCRESAHA.108.184382
© 2008 American Heart Association, Inc.
Editorials |
What Underlies Endothelial Shear Sensing? The Matrix, of Course
From the Division of Pulmonary and Critical Care Medicine, The University of Texas Southwestern Medical Center, Dallas.
Correspondence to Dr Lance S. Terada, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390. E-mail lance.terada@utsouthwestern.edu
See related article, pages 671–679
Key Words: PAK1 • shear stress • mechanotransduction • reactive oxidants • matrix • integrins
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
A number of chronic vascular diseases preferentially arise in distinct zones of arterial conduits such as intracranial aneurysms, which occur inside regions of curvature or at bifurcations, and pulmonary plexiform lesions, which occur just beyond dichotomous branch points. The geometry of these shapes strongly suggests that fluid dynamics play a key role in the pathogenesis of these lesions. Early atheromas have long been known to develop in similar locations, which are predicted to experience severe dynamic perturbations in shear rates such as flow reversal and separation bubbles. One might expect that progression of intimal and subintimal lesions would further distort shear distribution, leading to propagation of the disease. Thus, atherosclerosis is perhaps the most common human disease strongly influenced by mechanical signals, one of perhaps many diseases of mechanosensation. What pathways are activated by shear, and how is this sensed?
The majority of arterial surfaces experience laminar flow, which is relatively continuous across time and space. Endothelium exposed to such laminar flow is relatively quiescent, and the transcriptome of continuously sheared endothelium demonstrates expression of genes promoting survival and suppression of genes associated with proliferation and inflammation.1 Conversely, disturbed flow activates a panel of inflammatory, apoptotic, and procoagulant genes, supporting the atherogenic nature of abnormal mechanical signals.2 Downstream of the actual mechanosensors, a number of kinase pathways appear important in activating such broad cellular responses, such as extracellular signal-regulated kinase (ERK)5 and AMP-activated protein kinase.3,4
Because cells anchor themselves to the underlying matrix to resist shear forces, integrins or associated
Related Article:
B Activation by Flow
Circ. Res. 2008 103: 671-679.