This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Davies, P. F. Articles by Helmke, B. P. Search for Related Content PubMed PubMed Citation Articles by Davies, P. F. Articles by Helmke, B. P. Related Collections Cell biology/structural biology Cell signalling/signal transduction Imaging Other Vascular biology

(Circulation Research. 2003;92:359.)
© 2003 American Heart Association, Inc.

Reviews

Spatial Microstimuli in Endothelial Mechanosignaling

Peter F. Davies, Jenny Zilberberg, Brian P. Helmke

From the Institute for Medicine and Engineering (P.F.D., J.Z.), Department of Pathology and Laboratory Medicine (P.F.D.), University of Pennsylvania, Philadelphia, Pa; Department of Biomedical Engineering (B.P.H.), University of Virginia, Charlottesville, Va.

Correspondence to Dr P.F. Davies, Institute for Medicine and Engineering, University of Pennsylvania, 1010 Vagelos Laboratories, 3340 Smith Walk, Philadelphia, PA 19104. E-mail pfd{at}pobox.upenn.edu

Descriptive and quantitative analyses of microstimuli in living endothelial cells strongly support an integrated mechanism of mechanotransduction regulated by the spatial organization of multiple structural and signaling networks. Endothelial responses to blood flow are regulated at multiple levels of organization extending over scales from vascular beds to single cells, subcellular structures, and individual molecules. Microstimuli at the cellular and subcellular levels exhibit temporal and spatial complexities that are increasingly accessible to measurement. We address the cell and subcellular physical interface between flow-related forces and biomechanical responses of the endothelial cell. Live cell imaging and computational analyses of structural dynamics, two important approaches to microstimulation at this scale, are briefly reviewed.

Key Words: mechanotransduction • endothelial cells • shear stress • cytoskeletal dynamics

This article has been cited by other articles:

				Y.-J. Chiu, E. McBeath, and K. Fujiwara Mechanotransduction in an extracted cell model: Fyn drives stretch- and flow-elicited PECAM-1 phosphorylation J. Cell Biol., August 25, 2008; 182(4): 753 - 763. [Abstract] [Full Text] [PDF]

				F. le Noble, C. Klein, A. Tintu, A. Pries, and I. Buschmann Neural guidance molecules, tip cells, and mechanical factors in vascular development Cardiovasc Res, May 1, 2008; 78(2): 232 - 241. [Abstract] [Full Text] [PDF]

				I. R. Buschmann, K. Lehmann, F. Le Noble, and on behalf of Art.Net. Physics Meets Molecules: Is Modulation of Shear Stress the Link to Vascular Prevention? Circ. Res., March 14, 2008; 102(5): 510 - 512. [Full Text] [PDF]

				V. K. Sidhaye, K. S. Schweitzer, M. J. Caterina, L. Shimoda, and L. S. King Shear stress regulates aquaporin-5 and airway epithelial barrier function PNAS, March 4, 2008; 105(9): 3345 - 3350. [Abstract] [Full Text] [PDF]

				A. J.G. Horrevoets Profilin-1: An Unexpected Molecule Linking Vascular Inflammation to the Actin Cytoskeleton Circ. Res., August 17, 2007; 101(4): 328 - 330. [Full Text] [PDF]

				R. M. Rao, L. Yang, G. Garcia-Cardena, and F. W. Luscinskas Endothelial-Dependent Mechanisms of Leukocyte Recruitment to the Vascular Wall Circ. Res., August 3, 2007; 101(3): 234 - 247. [Abstract] [Full Text] [PDF]

				J. Seebach, G. Donnert, R. Kronstein, S. Werth, B. Wojciak-Stothard, D. Falzarano, C. Mrowietz, S. W. Hell, and H.-J. Schnittler Regulation of endothelial barrier function during flow-induced conversion to an arterial phenotype Cardiovasc Res, August 1, 2007; 75(3): 598 - 607. [Abstract] [Full Text] [PDF]

				A. Voorhees, G. B Nackman, and T. Wei Experiments show importance of flow-induced pressure on endothelial cell shape and alignment Proc R Soc A, June 8, 2007; 463(2082): 1409 - 1419. [Abstract] [Full Text] [PDF]

				C. Wagner, C. de Wit, L. Kurtz, C. Grunberger, A. Kurtz, and F. Schweda Connexin40 Is Essential for the Pressure Control of Renin Synthesis and Secretion Circ. Res., March 2, 2007; 100(4): 556 - 563. [Abstract] [Full Text] [PDF]

				M. P. Fautsch, D. H. Johnson, and the Second ARVO/Pfizer Research Institute Working Aqueous humor outflow: what do we know? Where will it lead us? Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4181 - 4187. [Full Text] [PDF]

				S. A. Wright, F. M. O'Prey, D. J. Rea, R. D. Plumb, A. J. Gamble, W. J. Leahey, A. B. Devine, R. C. McGivern, D. G. Johnston, M. B. Finch, et al. Microcirculatory Hemodynamics and Endothelial Dysfunction in Systemic Lupus Erythematosus Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2281 - 2287. [Abstract] [Full Text] [PDF]

				C. Friedrich, N. Endlich, W. Kriz, and K. Endlich Podocytes are sensitive to fluid shear stress in vitro Am J Physiol Renal Physiol, October 1, 2006; 291(4): F856 - F865. [Abstract] [Full Text] [PDF]

				D. D'Arcangelo, V. Ambrosino, M. Giannuzzo, C. Gaetano, and M. C. Capogrossi Axl receptor activation mediates laminar shear stress anti-apoptotic effects in human endothelial cells Cardiovasc Res, September 1, 2006; 71(4): 754 - 763. [Abstract] [Full Text] [PDF]

				K. N. Dahl, P. Scaffidi, M. F. Islam, A. G. Yodh, K. L. Wilson, and T. Misteli Distinct structural and mechanical properties of the nuclear lamina in Hutchinson-Gilford progeria syndrome PNAS, July 5, 2006; 103(27): 10271 - 10276. [Abstract] [Full Text] [PDF]

				H. Oberleithner, C. Riethmuller, T. Ludwig, V. Shahin, C. Stock, A. Schwab, M. Hausberg, K. Kusche, and H. Schillers Differential action of steroid hormones on human endothelium. J. Cell Sci., May 1, 2006; 119(Pt 9): 1926 - 1932. [Abstract] [Full Text] [PDF]

				R. L. Armentano, J. G. Barra, D. B. Santana, F. M. Pessana, S. Graf, D. Craiem, L. M. Brandani, H. P. Baglivo, and R. A. Sanchez Smart Damping Modulation of Carotid Wall Energetics in Human Hypertension: Effects of Angiotensin-Converting Enzyme Inhibition Hypertension, March 1, 2006; 47(3): 384 - 390. [Abstract] [Full Text] [PDF]

				E. A. Osborn, A. Rabodzey, C. F. Dewey Jr., and J. H. Hartwig Endothelial actin cytoskeleton remodeling during mechanostimulation with fluid shear stress Am J Physiol Cell Physiol, February 1, 2006; 290(2): C444 - C452. [Abstract] [Full Text] [PDF]

				J. D. Pearson Tightening the Barrier: Mechanical Forces and the Control of Endothelial Permeability Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 10 - 11. [Full Text] [PDF]

				M. Dixit, A. E. Loot, A. Mohamed, B. Fisslthaler, C. M. Boulanger, B. Ceacareanu, A. Hassid, R. Busse, and I. Fleming Gab1, SHP2, and Protein Kinase A Are Crucial for the Activation of the Endothelial NO Synthase by Fluid Shear Stress Circ. Res., December 9, 2005; 97(12): 1236 - 1244. [Abstract] [Full Text] [PDF]

				S. L. Cuvelier, S. Paul, N. Shariat, P. Colarusso, and K. D. Patel Eosinophil adhesion under flow conditions activates mechanosensitive signaling pathways in human endothelial cells J. Exp. Med., September 19, 2005; 202(6): 865 - 876. [Abstract] [Full Text] [PDF]

				I. Fleming, B. Fisslthaler, M. Dixit, and R. Busse Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells J. Cell Sci., September 15, 2005; 118(18): 4103 - 4111. [Abstract] [Full Text] [PDF]

				R. Zaidel-Bar, Z. Kam, and B. Geiger Polarized downregulation of the paxillin-p130CAS-Rac1 pathway induced by shear flow J. Cell Sci., September 1, 2005; 118(17): 3997 - 4007. [Abstract] [Full Text] [PDF]

				N. W. Blackstone and D. M. Bridge Model Systems for Environmental Signaling Integr. Comp. Biol., August 1, 2005; 45(4): 605 - 614. [Abstract] [Full Text] [PDF]

				J. C. R. Jones, K. Lane, S. B. Hopkinson, E. Lecuona, R. C. Geiger, D. A. Dean, E. Correa-Meyer, M. Gonzales, K. Campbell, J. I. Sznajder, et al. Laminin-6 assembles into multimolecular fibrillar complexes with perlecan and participates in mechanical-signal transduction via a dystroglycan-dependent, integrin-independent mechanism J. Cell Sci., June 15, 2005; 118(12): 2557 - 2566. [Abstract] [Full Text] [PDF]

				D. Lominadze, N. Tsakadze, U. Sen, J. C. Falcone, and S. E. D'Souza Fibrinogen and fragment D-induced vascular constriction Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1257 - H1264. [Abstract] [Full Text] [PDF]

				H. A. Silber, P. Ouyang, D. A. Bluemke, S. N. Gupta, T. K. Foo, and J. A. C. Lima Why is flow-mediated dilation dependent on arterial size? Assessment of the shear stimulus using phase-contrast magnetic resonance imaging Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H822 - H828. [Abstract] [Full Text] [PDF]

				P. A. VanderLaan, C. A. Reardon, and G. S. Getz Site Specificity of Atherosclerosis: Site-Selective Responses to Atherosclerotic Modulators Arterioscler Thromb Vasc Biol, January 1, 2004; 24(1): 12 - 22. [Abstract] [Full Text] [PDF]

				R. T. Lee Lessons From Lymph: Flow-Guided Vessel Formation Circ. Res., April 18, 2003; 92(7): 701 - 703. [Full Text] [PDF]