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The FASEB Journal, Vol 9, 874-882, Copyright © 1995 by The Federation of American Societies for Experimental Biology


REVIEWS

Hemodynamic forces are complex regulators of endothelial gene expression

N Resnick and MA Gimbrone Jr
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115-5817, USA.

Vascular endothelial cells, by virtue of their unique anatomical position, are constantly exposed to the fluid mechanical forces generated by flowing blood. In vitro studies with model flow systems have demonstrated that wall shear stresses can modulate various aspects of endothelial structure and function. Certain of these effects appear to result from the regulation of expression of endothelial genes at the transcriptional level. Recent molecular biological studies have defined a "shear stress response element" (SSRE) in the promoter of the human platelet-derived growth factor (PDGF)-B chain gene that interacts with DNA binding proteins in the nuclei of shear-stressed endothelial cells to up-regulate transcriptional activity. Insertion of this element into reporter genes also renders them shear-inducible. Further characterization of this and other positive (and negative) shear- responsive genetic regulatory elements, as well as their transactivating factors, should enhance our understanding of vascular endothelium as an integrator of humoral and biomechanical stimuli in health and disease.


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T. Nagel, N. Resnick, C. F. Dewey Jr, and M. A. Gimbrone Jr
Vascular Endothelial Cells Respond to Spatial Gradients in Fluid Shear Stress by Enhanced Activation of Transcription Factors
Arterioscler Thromb Vasc Biol, August 1, 1999; 19(8): 1825 - 1834.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
M. D. Silverman, C. R. Waters, G. T. Hayman, J. Wigboldus, M. M. Samet, and P. I. Lelkes
Tissue factor activity is increased in human endothelial cells cultured under elevated static pressure
Am J Physiol Cell Physiol, August 1, 1999; 277(2): C233 - C242.
[Abstract] [Full Text] [PDF]


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Am. J. Pathol.Home page
M. A. Gimbrone Jr.
Vascular Endothelium, Hemodynamic Forces, and Atherogenesis
Am. J. Pathol., July 1, 1999; 155(1): 1 - 5.
[Full Text] [PDF]


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Am. J. Pathol.Home page
T. Zand, A. H. Hoffman, B. J. Savilonis, J. M. Underwood, J. J. Nunnari, G. Majno, and I. Joris
Lipid Deposition in Rat Aortas with Intraluminal Hemispherical Plug Stenosis : A Morphological and Biophysical Study
Am. J. Pathol., July 1, 1999; 155(1): 85 - 92.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
T. Gloe, S. Riedmayr, H.-Y. Sohn, and U. Pohl
The 67-kDa Laminin-binding Protein Is Involved in Shear Stress-dependent Endothelial Nitric-oxide Synthase Expression
J. Biol. Chem., June 4, 1999; 274(23): 15996 - 16002.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
H. Morawietz, Y.-H. Ma, F. Vives, E. Wilson, V. P. Sukhatme, J. Holtz, and H. E. Ives
Rapid Induction and Translocation of Egr-1 in Response to Mechanical Strain in Vascular Smooth Muscle Cells
Circ. Res., April 2, 1999; 84(6): 678 - 687.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
P. Clarkson, H. E. Montgomery, M. J. Mullen, A. E. Donald, A. J. Powe, T. Bull, M. Jubb, M. World, and J. E. Deanfield
Exercise training enhances endothelial function in young men
J. Am. Coll. Cardiol., April 1, 1999; 33(5): 1379 - 1385.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
X. Bao, C. Lu, and J. A. Frangos
Temporal Gradient in Shear But Not Steady Shear Stress Induces PDGF-A and MCP-1 Expression in Endothelial Cells : Role of NO, NF{kappa}B, and egr-1
Arterioscler Thromb Vasc Biol, April 1, 1999; 19(4): 996 - 1003.
[Abstract] [Full Text] [PDF]


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Cardiovasc ResHome page
J. E. Bishop and G. Lindahl
Regulation of cardiovascular collagen synthesis by mechanical load
Cardiovasc Res, April 1, 1999; 42(1): 27 - 44.
[Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
N. DePaola, P. F. Davies, W. F. Pritchard Jr., L. Florez, N. Harbeck, and D. C. Polacek
Spatial and temporal regulation of gap junction connexin43 in vascular endothelial cells exposed to controlled disturbed flows in vitro
PNAS, March 16, 1999; 96(6): 3154 - 3159.
[Abstract] [Full Text] [PDF]


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CirculationHome page
M. Gosling, J. Golledge, R. J. Turner, and J. T. Powell
Arterial Flow Conditions Downregulate Thrombomodulin on Saphenous Vein Endothelium
Circulation, March 2, 1999; 99(8): 1047 - 1053.
[Abstract] [Full Text] [PDF]


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DevelopmentHome page
A. Meeson, M Argilla, K Ko, L Witte, and R. Lang
VEGF deprivation-induced apoptosis is a component of programmed capillary regression
Development, January 4, 1999; 126(7): 1407 - 1415.
[Abstract] [PDF]


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Am. J. Physiol. Cell Physiol.Home page
M. Nakao, K. Ono, S. Fujisawa, and T. Iijima
Mechanical stress-induced Ca2+ entry and Cl- current in cultured human aortic endothelial cells
Am J Physiol Cell Physiol, January 1, 1999; 276(1): C238 - C249.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
V. Rizzo, D. P. McIntosh, P. Oh, and J. E. Schnitzer
In Situ Flow Activates Endothelial Nitric Oxide Synthase in Luminal Caveolae of Endothelium with Rapid Caveolin Dissociation and Calmodulin Association
J. Biol. Chem., December 25, 1998; 273(52): 34724 - 34729.
[Abstract] [Full Text] [PDF]


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BloodHome page
C. Rius, J. D. Smith, N. Almendro, C. Langa, L. M. Botella, D. A. Marchuk, C. P.H. Vary, and C. Bernabeu
Cloning of the Promoter Region of Human Endoglin, the Target Gene for Hereditary Hemorrhagic Telangiectasia Type 1
Blood, December 15, 1998; 92(12): 4677 - 4690.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. Pugin, I. Dunn, P. Jolliet, D. Tassaux, J.-L. Magnenat, L. P. Nicod, and J.-C. Chevrolet
Activation of human macrophages by mechanical ventilation in vitro
Am J Physiol Lung Cell Mol Physiol, December 1, 1998; 275(6): L1040 - L1050.
[Abstract] [Full Text] [PDF]


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CirculationHome page
J. N. Topper, J. Cai, G. Stavrakis, K. R. Anderson, E. A. Woolf, B. A. Sampson, F. J. Schoen, D. Falb, and M. A. Gimbrone Jr
Human Prostaglandin Transporter Gene (hPGT) is Regulated by Fluid Mechanical Stimuli in Cultured Endothelial Cells and Expressed in Vascular Endothelium in Vivo
Circulation, December 1, 1998; 98(22): 2396 - 2403.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Heart Circ. Physiol.Home page
S. M. Black, J. R. Fineman, R. H. Steinhorn, J. Bristow, and S. J. Soifer
Increased endothelial NOS in lambs with increased pulmonary blood flow and pulmonary hypertension
Am J Physiol Heart Circ Physiol, November 1, 1998; 275(5): H1643 - H1651.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
V. Rizzo, A. Sung, P. Oh, and J. E. Schnitzer
Rapid Mechanotransduction in Situ at the Luminal Cell Surface of Vascular Endothelium and Its Caveolae
J. Biol. Chem., October 9, 1998; 273(41): 26323 - 26329.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
E. V. Vitvitsky, J. P. Griffin, M. H. Collins, T. L. Spray, and J. W. Gaynor
Increased pulmonary blood flow produces endothelial cell dysfunction in neonatal swine
Ann. Thorac. Surg., October 1, 1998; 66(4): 1372 - 1377.
[Abstract] [Full Text] [PDF]


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Am. J. Pathol.Home page
Y. Zou, H. Dietrich, Y. Hu, B. Metzler, G. Wick, and Q. Xu
Mouse Model of Venous Bypass Graft Arteriosclerosis
Am. J. Pathol., October 1, 1998; 153(4): 1301 - 1310.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
J. E. Gabriels and D. L. Paul
Connexin43 Is Highly Localized to Sites of Disturbed Flow in Rat Aortic Endothelium but Connexin37 and Connexin40 Are More Uniformly Distributed
Circ. Res., September 21, 1998; 83(6): 636 - 643.
[Abstract] [Full Text] [PDF]


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FASEB J.Home page
Y. Hu, G. Böck, G. Wick, and Q. Xu
Activation of PDGF receptor {alpha} in vascular smooth muscle cells by mechanical stress
FASEB J, September 1, 1998; 12(12): 1135 - 1142.
[Abstract] [Full Text]


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Physiol. Rev.Home page
P. A. JANMEY
The Cytoskeleton and Cell Signaling: Component Localization and Mechanical Coupling
Physiol Rev, July 1, 1998; 78(3): 763 - 781.
[Abstract] [Full Text] [PDF]


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Am. J. Respir. Crit. Care Med.Home page
A. S. SLUTSKY and L. N. TREMBLAY
Multiple System Organ Failure . Is Mechanical Ventilation a Contributing Factor?
Am. J. Respir. Crit. Care Med., June 1, 1998; 157(6): 1721 - 1725.
[Full Text] [PDF]


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BloodHome page
Y. Matsumoto, Y. Kawai, K. Watanabe, K. Sakai, M. Murata, M. Handa, S. Nakamura, and Y. Ikeda
Fluid Shear Stress Attenuates Tumor Necrosis Factor-alpha -Induced Tissue Factor Expression in Cultured Human Endothelial Cells
Blood, June 1, 1998; 91(11): 4164 - 4172.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
T. Ziegler, K. Bouzourene, V. J. Harrison, H. R. Brunner, and D. Hayoz
Influence of Oscillatory and Unidirectional Flow Environments on the Expression of Endothelin and Nitric Oxide Synthase in Cultured Endothelial Cells
Arterioscler Thromb Vasc Biol, May 1, 1998; 18(5): 686 - 692.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
D. B. Cowan, S. J. Lye, and B. L. Langille
Regulation of Vascular Connexin43 Gene Expression by Mechanical Loads
Circ. Res., April 20, 1998; 82(7): 786 - 793.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
B. E. Sumpio, W. Du, G. Galagher, X.-j. Wang, L. M. Khachigian, T. Collins, M. A. Gimbrone Jr, and N. Resnick
Regulation of PDGF-B in Endothelial Cells Exposed to Cyclic Strain
Arterioscler Thromb Vasc Biol, March 1, 1998; 18(3): 349 - 355.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. A. Gutierrez, R. F. Gonzalez, and L. G. Dobbs
Mechanical distension modulates pulmonary alveolar epithelial phenotypic expression in vitro
Am J Physiol Lung Cell Mol Physiol, February 1, 1998; 274(2): L196 - L202.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
S. Chien, S. Li, and J. Y-J. Shyy
Effects of Mechanical Forces on Signal Transduction and Gene Expression in Endothelial Cells
Hypertension, January 1, 1998; 31(1): 162 - 169.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
E. Wilson, F. Vives, T. Collins, and H. E. Ives
Strain-Responsive Regions in the Platelet-Derived Growth Factor-A Gene Promoter
Hypertension, January 1, 1998; 31(1): 170 - 175.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
Y. Liu, K. Pleyte, H.-G. Knaus, and N. J. Rusch
Increased Expression of Ca2+-Sensitive K+ Channels in Aorta of Hypertensive Rats
Hypertension, December 1, 1997; 30(6): 1403 - 1409.
[Abstract] [Full Text]




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