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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				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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				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]