Concluding Remarks

Shear stress and tensile forces are now well recognized as factors that regulate endothelial signaling, cytoskeletal remodeling, gene expression, and physiological responses. A rapidly growing body of evidence indicates that endothelial cell discriminate between laminar and spatial gradients of shear stress, steady and pulsatile laminar flow, and low-and high-amplitude cyclic stretch. Moreover, the pattern of mechanical stimulation determines whether endothelial cells will develop pro- or anti-inflammatory cell response and also may differentially regulate endothelial barrier properties (Figure 2). Experimental and analytical tools are being developed to assess the stress distribution throughout cell structures that might be involved in mechanotransduction. Further studies will address the role of specific patterns of mechanical forces experienced by endothelium in physiological and pathological conditions (acute injury, inflammation, hypertension, ventilator-induced lung injury) and will identify key cellular targets for drug design and gene therapy.


Mechanical strain or stretch: Change in length in relation to initial length.

Shear stress: Force per unit surface area in the direction of flow exerted at the fluid-surface interface. Stress: Force per unit area.


1. Tschumperlin, D. J., and Margulies, S. S. (1999). Alveolar epithelial surface area-volume relationship in isolated rat lungs. J. Appl. Physiol. 86, 2026-2033.

2. Birukov, K. G., Jacobson, J. R., Flores, A. A., Ye, S. Q., Birukova, A. A., Verin, A. D., and Garcia, J. G. (2003). Magnitude-dependent regulation of pulmonary endothelial cell barrier function by cyclic stretch. Am. J. Physiol. Lung Cell. Mol. Physiol. 285(4), L785-L797.

3. Dos Santos, C. C., and Slutsky, A. S. (2000). Invited review: Mechanisms of ventilator-induced lung injury: A perspective. J. Appl. Physiol. 89, 1645-1655.

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5. Vlahakis, N. E., Schroeder, M. A., Limper, A. H., and Hubmayr, R. D. (1999). Stretch induces cytokine release by alveolar epithelial cells in vitro. Am. J. Physiol. 277, L167-L173.

6. Davies, P. F. (1995). Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75, 519-560. This is a comprehensive review of endothe-lial biology under shear stress, which summarizes data about putative mechanosensors and signaling pathways and describes sequence of cellular events in response to flow from activation of flow-sensitive ion channels and second messenger signaling systems to cytoskeletal remodeling and regulation of gene expression.

7. Shyy, J. Y., and Chien, S. (2002). Role of integrins in endothelial mechanosensing of shear stress. Circ. Res. 91, 769-775. This review shows a role for integrin-dependent signaling via downstream activation of protein tyrosine kinases in mechanotransduction.

8. Brooks, A. R., Lelkes, P. I., and Rubanyi, G. M. (2002). Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow. Physiol. Genomics 9, 27-41.

9. Chen, B. P., Li, Y. S., Zhao, Y., Chen, K. D., Li, S., Lao, J., Yuan, S., Shyy, J. Y., and Chien, S. (2001). DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress. Phys-iol. Genomics 7, 55-63. This study demonstrates transactivation of growth factor receptor tyrosine kinases by mechanical forces. This mechanism converges signaling pathways triggered by mechanical and chemical factors.

10. Garcia-Cardena, G., Comander, J., Anderson, K. R., Blackman, B. R., and Gimbrone, M. A., Jr. (2001). Biomechanical activation of vascular endothelium as a determinant of its functional phenotype. Proc. Natl. Acad. Sci. USA 98, 4478-4485. This is the first gene profiling report on the effects of laminar and disturbed shear stress in EC cultures.

11. McCormick, S. M., Eskin, S. G., McIntire, L. V., Teng, C. L., Lu, C. M., Russell, C. G., and Chittur, K. K. (2001). DNA microarray reveals changes in gene expression of shear stressed human umbilical vein endothelial cells. Proc. Natl. Acad. Sci. USA 98, 8955-8960.

Capsule Biography

Dr. Konstantin Birukov has been studying the role of mechanical factors in vascular endothelial and smooth muscle cell biology since 1989. His group primarily focuses on mechanochemical regulation of signaling, phe-notypic expression and endothelial permeability. His work is supported by grants from the NHLBI and NIH (HL075349, HL076259).

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