Abstract
Endothelial cells, because of their unique localization, are constantly exposed to fluid mechanical forces derived by the flowing blood. These forces, and more specifically shear stresses, affect endothelial structure and function, both in vivo and in vitro, and are implicated as contributing factors in the development of cardiovascular diseases. We have demonstrated earlier that the shear stress selectively induces the transcription of several endothelial genes, and have defined a shear stress response element (SSRE) in the promoter of platelet-derived-growth-factor B (PDGF-B), that is shared by additional endothelial shear stress responsive genes. Here we further characterize this SSRE and the nuclear factors that bind to it, and imply the possible role of the endothelium cytoskeleton in transducing shear stress, leading to the expression of PDGF-B/SSRE constructs in transfected endothelial cells exposed to shear stress. We also present, yet a new shear stress response element in the Platelet Derived Growth Factor A promoter, that contains a binding site to the transcription factors egr1/sp1. These results further demonstrate the complexity of gene regulation by hemodynamic forces, and support the important part that these forces have in the physiology and pathophysiology of the vessel wall.
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References
Frangos JA ed. Physical forces and the mammalian cell. Academic Press, San Diego, CA, 1993.
Caro CG, Fitz-Gerald JM, Schorter RC. Atheroma and arterial wall shear: Observation, correlation and proposal of shear dependent mass transfer mechanism for atherogenesis. Proc Natl Acad Sci USA 1971;177:109–159.
Ku DN, Giddens DP, Zarins CK, Galgov S. Pulsatile flow and atherosclerosis in the human carotid bifurcation: positive correlation between plaque location and low and oscillating shear stress. Arteriosclerosis 1985;5:293–302.
Resnick N and Gimbrone MA Jr. Hemodynamic forces are complex regulators of endothelial gene expression. FASEB J 1995;9:874–882.
Davies PF. Flow mediated endothelial mechanotransduction. Physiol Rev 1995;75:519–560.
Resnick N, Collins T, Atkinson W, Bonthron DT, Dewey FC Jr, Gimbrone MA Jr. Platelet derived, growth factor B chain promoter contains a cis-acting fluid shear-stress-responsive element. Proc Natl Acad Sci USA 1993;90:4591–4595.
Resnick N, Sumpio BE, Gimbrone MA Jr. Endothelial gene regulation by biomechanical forces. In: Woodford FP, Davignon J, Sniderman A, eds. Proceedings of the Xth International Symposium on Atherosclerosis. Montreal, Quebec. Elsevier, NY. 1994;838–843.
Khachigian LM, Resnick R, Gimbrone MA Jr, Collins T. Nuclear factor kB interacts functionally with the platelet derived growth factor B chain shear stress response element in vascular endothelial cells exposed to fluid shear stress. J Clin Invest 1995;96:1169–1175.
Bussolari SR, Dewey CF Jr, Gimbrone MA Jr. Apparatus for subjecting living cells to fluid shear stress. Rev Sci Instrum 1982;53:1851–1854.
Lan Q, Mercurius KO, Davies PF. Stimulation of transcriptional factors NFkB and AP1 in endothelial cells subjected to shear stress. Biochem Biophys Res Commun 1994;201:950–956.
Rosette C, Karin M. Cytoskeletal control of gene expression: depolymerization of microtubules activates NFkB. J Cell Biol 1995;6:1111–1119.
Hsieh HJ, Li NQ, Frangos JA. Shear stress increases endothelial platelet derived growth factor messenger RNA levels. Am J Physiol 1991;260:H642–646.
Hanlon NJ, Collins T, Gimbrone MA Jr, Resnick N. Regulation of the endothelial PDGF-A gene by shear stress. Circulation 1994;IV468 (abstract).
Khachigian LM, Lindner V, Williams AJ and Collins T. Egr-1 induced endothelial gene expression: A common theme in vascular injury. Science 1996;271:1427–1431.
Sumpio BE ed: Hemodynamic Forces and Vascular Cell Biology. RG Landes Company, Austin, TX, USA. 1993.
Nagel T, Resnick N, Atkinson WJ, Dewey CF Jr, Gimbrone MA Jr. Shear stress selectively upregulates intercellular adhesion molecule 1 expression in cultured human vascular endothelial cells. J Clin Invest 1994;94:885–891.
Lewis H, Kaszubska W, Delamarter JF, Whealan J. Cooperativity between two NFkB complexes mediated by high-mobility-group proteins 1(Y) is essential for cytokine-induced expression of the E-selectin promoter. Mol Cell Biol 1994;14:5701–5709.
Fujita T, Nolan GP, Gosh S, Baltimore D. Independent modes of transcriptional activation by the p50 and p65 subunits of NFkB. Genes & Dev 1992;6:775–787.
Collins T, Read MA, Neish AS, Whitley MZ, Thanos D, Maniatis T. Transcriptional regulation of endothelial cells adhesion molecules: NFkB and cytokine-inducible enhancers. FASEB J 1995;9:883–893.
Neish A, Read MA, Thanos D, Pine R, Maniatis T, Collins T. Endothelial interferon regulatory factor-1 cooperates with NFkB as a transcriptional activator of vascular cell adhesion molecule 1. Mol Cell Biol 1995;15:2558–2569.
Morita T, Kurihara H, Maemura K, Yoshizumi M, Yazaki Y. Disruption of cytoskeletal structure mediates shear stress-induced endothelin-1 gene expression in cultured porcine aortic endothelial cells. J Clin Invest 1993;92:1706–1712.
Shyy Y, Hsieh HJ, Usami S, Chien S. Fluid shear stress induces a biphasic response of human monocyte chemotactic protein 1 gene expression in vascular endothelium. Proc Natl Acad Sci 1994;91:4678–4682.
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© 1997 Springer Science+Business Media New York
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Resnick, N. et al. (1997). Endothelial Gene Regulation by Laminar Shear Stress. In: Sideman, S., Beyar, R. (eds) Analytical and Quantitative Cardiology. Advances in Experimental Medicine and Biology, vol 430. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5959-7_13
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DOI: https://doi.org/10.1007/978-1-4615-5959-7_13
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