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 Feng, Y. Articles by Lee, R. T. Search for Related Content PubMed PubMed Citation Articles by Feng, Y. Articles by Lee, R. T.

(Circulation Research. 1999;85:1118.)
© 1999 American Heart Association, Inc.

Molecular Medicine

Transcriptional Profile of Mechanically Induced Genes in Human Vascular Smooth Muscle Cells

Yajun Feng, Jeong-Hee Yang, Hayden Huang, Scott P. Kennedy, Thomas G. Turi, John F. Thompson, Peter Libby, Richard T. Lee

From the Vascular Medicine and Atherosclerosis Unit (Y.F., J.-H.Y., H.H., P.L., R.T.L.), Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Pfizer Central Research (S.P.K., T.G.T., J.F.T.), Groton, Conn.

Correspondence to Richard T. Lee, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail rtlee{at}bics.bwh.harvard.edu

Abstract—Vascular smooth muscle cells must monitor and respond to their mechanical environment; however, the molecular response of these cells to mechanical stimuli remains incompletely defined. By applying a highly uniform biaxial cyclic strain to cultured cells, we used DNA microarray technology to describe the transcriptional profile of mechanically induced genes in human aortic smooth muscle cells. We first identified vascular endothelial growth factor (VEGF) as a mechanically induced gene in these cells; VEGF served as a positive control for these experiments. We then used a DNA microarray with 5000 genes with putative functions to identify additional mechanically induced genes. Surprisingly, relatively few genes are mechanically induced in human aortic smooth muscle cells. Only 3 transcripts of 5000 were induced >2.5-fold: cyclooxygenase-1, tenascin-C, and plasminogen activator inhibitor-1. Downregulated transcripts included matrix metalloproteinase-1 and thrombomodulin. The transcriptional profile of mechanically induced genes in human aortic smooth muscle cells suggests a response of defense against excessive deformation. These data also demonstrate that in addition to identifying large clusters of genes that respond to a given stimulus, DNA microarray technology may be used to identify a small subset of genes that comprise a highly specific molecular response.

Key Words: vascular smooth muscle • genomics • strain

This article has been cited by other articles:

				F. G. Spinale Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function Physiol Rev, October 1, 2007; 87(4): 1285 - 1342. [Abstract] [Full Text] [PDF]

				V. Gupta and K. J. Grande-Allen Effects of static and cyclic loading in regulating extracellular matrix synthesis by cardiovascular cells Cardiovasc Res, December 1, 2006; 72(3): 375 - 383. [Abstract] [Full Text] [PDF]

				V. de Waard, E. K. Arkenbout, M. Vos, A. I.M. Mocking, H. W.M. Niessen, W. Stooker, B. A.J.M. de Mol, P. H.A. Quax, E. N.T.P. Bakker, E. VanBavel, et al. TR3 Nuclear Orphan Receptor Prevents Cyclic Stretch-Induced Proliferation of Venous Smooth Muscle Cells Am. J. Pathol., June 1, 2006; 168(6): 2027 - 2035. [Abstract] [Full Text] [PDF]

				R. S. Vasan Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations Circulation, May 16, 2006; 113(19): 2335 - 2362. [Full Text] [PDF]

				J. G. Abraldes, Y. Iwakiri, M. Loureiro-Silva, O. Haq, W. C. Sessa, and R. J. Groszmann Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state Am J Physiol Gastrointest Liver Physiol, May 1, 2006; 290(5): G980 - G987. [Abstract] [Full Text] [PDF]

				M. E. Davis, P. C.H. Hsieh, A. J. Grodzinsky, and R. T. Lee Custom Design of the Cardiac Microenvironment With Biomaterials Circ. Res., July 8, 2005; 97(1): 8 - 15. [Abstract] [Full Text] [PDF]

				E. Lutgens, B. Faber, K. Schapira, C. T.A. Evelo, R. van Haaften, S. Heeneman, K. B.J.M. Cleutjens, A. P. Bijnens, L. Beckers, J. G. Porter, et al. Gene Profiling in Atherosclerosis Reveals a Key Role for Small Inducible Cytokines: Validation Using a Novel Monocyte Chemoattractant Protein Monoclonal Antibody Circulation, June 28, 2005; 111(25): 3443 - 3452. [Abstract] [Full Text] [PDF]

				S. R. Frye, A. Yee, S. G. Eskin, R. Guerra, X. Cong, and L. V. McIntire cDNA microarray analysis of endothelial cells subjected to cyclic mechanical strain: importance of motion control Physiol Genomics, March 21, 2005; 21(1): 124 - 130. [Abstract] [Full Text] [PDF]

				R. M. Adam, S. H. Eaton, C. Estrada, A. Nimgaonkar, S.-C. Shih, L. E. H. Smith, I. S. Kohane, D. Bagli, and M. R. Freeman Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells Physiol Genomics, December 15, 2004; 20(1): 36 - 44. [Abstract] [Full Text] [PDF]

				H. Moriwaki, A. Stempien-Otero, M. Kremen, A. E. Cozen, and D. A. Dichek Overexpression of Urokinase by Macrophages or Deficiency of Plasminogen Activator Inhibitor Type 1 Causes Cardiac Fibrosis in Mice Circ. Res., September 17, 2004; 95(6): 637 - 644. [Abstract] [Full Text] [PDF]

				P. Lacolley Mechanical influence of cyclic stretch on vascular endothelial cells Cardiovasc Res, September 1, 2004; 63(4): 577 - 579. [Full Text] [PDF]

				H. Huang, R. D. Kamm, and R. T. Lee Cell mechanics and mechanotransduction: pathways, probes, and physiology Am J Physiol Cell Physiol, July 1, 2004; 287(1): C1 - C11. [Abstract] [Full Text] [PDF]

				M. V. Podgoreanu and D. A. Schwinn Genomics and the circulation Br. J. Anaesth., July 1, 2004; 93(1): 140 - 148. [Abstract] [Full Text] [PDF]

				M. Cattaruzza, C. Lattrich, and M. Hecker Focal Adhesion Protein Zyxin Is a Mechanosensitive Modulator of Gene Expression in Vascular Smooth Muscle Cells Hypertension, April 1, 2004; 43(4): 726 - 730. [Abstract] [Full Text] [PDF]

				S. Lehoux and A. Tedgui All Strain, No Gain: Stretch Keeps Proliferation at Bay via the NF-{kappa}B Response Gene iex-1 Circ. Res., December 12, 2003; 93(12): 1139 - 1141. [Full Text] [PDF]

				P. C. Schulze, G. W. de Keulenaer, K. A. Kassik, T. Takahashi, Z. Chen, D. I. Simon, and R. T. Lee Biomechanically Induced Gene iex-1 Inhibits Vascular Smooth Muscle Cell Proliferation and Neointima Formation Circ. Res., December 12, 2003; 93(12): 1210 - 1217. [Abstract] [Full Text] [PDF]

				K. G. Birukov, J. R. Jacobson, A. A. Flores, S. Q. Ye, A. A. Birukova, A. D. Verin, and J. G. N. Garcia Magnitude-dependent regulation of pulmonary endothelial cell barrier function by cyclic stretch Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L785 - L797. [Abstract] [Full Text] [PDF]

				C. M. Milner and A. J. Day TSG-6: a multifunctional protein associated with inflammation J. Cell Sci., May 15, 2003; 116(10): 1863 - 1873. [Abstract] [Full Text] [PDF]

				T. A. H. Jarvinen, L. Jozsa, P. Kannus, T. L. N. Jarvinen, T. Hurme, M. Kvist, M. Pelto-Huikko, H. Kalimo, and M. Jarvinen Mechanical loading regulates the expression of tenascin-C in the myotendinous junction and tendon but does not induce de novo synthesis in the skeletal muscle J. Cell Sci., March 1, 2003; 116(5): 857 - 866. [Abstract] [Full Text] [PDF]

				J. L. Sperry, C. B. Deming, C. Bian, P. L. Walinsky, D. A. Kass, F. D. Kolodgie, R. Virmani, A. Y. Kim, and J. J. Rade Wall Tension Is a Potent Negative Regulator of In Vivo Thrombomodulin Expression Circ. Res., January 10, 2003; 92(1): 41 - 47. [Abstract] [Full Text] [PDF]

				T. K. Nakahashi, K. Hoshina, P. S. Tsao, E. Sho, M. Sho, J. K. Karwowski, C. Yeh, R.-B. Yang, J. N. Topper, and R. L. Dalman Flow Loading Induces Macrophage Antioxidative Gene Expression in Experimental Aneurysms Arterioscler Thromb Vasc Biol, December 1, 2002; 22(12): 2017 - 2022. [Abstract] [Full Text] [PDF]

				H. Inoue, Y. Taba, Y. Miwa, C. Yokota, M. Miyagi, and T. Sasaguri Transcriptional and Posttranscriptional Regulation of Cyclooxygenase-2 Expression by Fluid Shear Stress in Vascular Endothelial Cells Arterioscler Thromb Vasc Biol, September 1, 2002; 22(9): 1415 - 1420. [Abstract] [Full Text] [PDF]

				Y. Wang, G. W. De Keulenaer, E. O. Weinberg, S. Muangman, A. Gualberto, K. T. Landschulz, T. G. Turi, J. F. Thompson, and R. T. Lee Direct biomechanical induction of endogenous calcineurin inhibitor Down Syndrome Critical Region-1 in cardiac myocytes Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H533 - H539. [Abstract] [Full Text] [PDF]

				D. Zagzag, B. Shiff, G. I. Jallo, M. A. Greco, C. Blanco, H. Cohen, J. Hukin, J. C. Allen, and D. R. Friedlander Tenascin-C Promotes Microvascular Cell Migration and Phosphorylation of Focal Adhesion Kinase Cancer Res., May 1, 2002; 62(9): 2660 - 2668. [Abstract] [Full Text] [PDF]

				P.A Henriksen and Y Kotelevtsev Application of gene expression profiling to cardiovascular disease Cardiovasc Res, April 1, 2002; 54(1): 16 - 24. [Abstract] [Full Text] [PDF]

				A. Y. Kim, P. L. Walinsky, F. D. Kolodgie, C. Bian, J. L. Sperry, C. B. Deming, E. A. Peck, J. G. Shake, G. B. Ang, R. H. Sohn, et al. Early Loss of Thrombomodulin Expression Impairs Vein Graft Thromboresistance: Implications for Vein Graft Failure Circ. Res., February 8, 2002; 90(2): 205 - 212. [Abstract] [Full Text] [PDF]

				R. Samarakoon and P. J. Higgins MEK/ERK pathway mediates cell-shape-dependent plasminogen activator inhibitor type 1 gene expression upon drug-induced disruption of the microfilament and microtubule networks J. Cell Sci., January 8, 2002; 115(15): 3093 - 3103. [Abstract] [Full Text] [PDF]

				K. Iida and I. Nishimura GENE EXPRESSION PROFILING BY DNA MICROARRAY TECHNOLOGY Critical Reviews in Oral Biology & Medicine, January 1, 2002; 13(1): 35 - 50. [Abstract] [Full Text] [PDF]

				L. Li and E. L. Chaikof Mechanical Stress Regulates Syndecan-4 Expression and Redistribution in Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 61 - 68. [Abstract] [Full Text] [PDF]

				P. L. Jones, R. Chapados, H. S. Baldwin, G. W. Raff, E. V. Vitvitsky, T. L. Spray, and J. W. Gaynor Altered hemodynamics controls matrix metalloproteinase activity and tenascin-C expression in neonatal pig lung Am J Physiol Lung Cell Mol Physiol, January 1, 2002; 282(1): L26 - L35. [Abstract] [Full Text] [PDF]

				K. T. Nguyen, S. R. Frye, S. G. Eskin, C. Patterson, M. S. Runge, and L. V. McIntire Cyclic Strain Increases Protease-Activated Receptor-1 Expression in Vascular Smooth Muscle Cells Hypertension, November 1, 2001; 38(5): 1038 - 1043. [Abstract] [Full Text] [PDF]

				J.-B. Michel Contrasting Outcomes of Atheroma Evolution: Intimal Accumulation Versus Medial Destruction Arterioscler Thromb Vasc Biol, September 1, 2001; 21(9): 1389 - 1392. [Full Text] [PDF]

				B. C. Berk Vascular Smooth Muscle Growth: Autocrine Growth Mechanisms Physiol Rev, July 1, 2001; 81(3): 999 - 1030. [Abstract] [Full Text] [PDF]

				D. Zohlnhofer, C. A. Klein, T. Richter, R. Brandl, A. Murr, T. Nuhrenberg, A. Schomig, P. A. Baeuerle, and F.-J. Neumann Gene Expression Profiling of Human Stent-Induced Neointima by cDNA Array Analysis of Microscopic Specimens Retrieved by Helix Cutter Atherectomy : Detection of FK506-Binding Protein 12 Upregulation Circulation, March 13, 2001; 103(10): 1396 - 1402. [Abstract] [Full Text] [PDF]

				J. N. Topper Genes, Matrix, and Restenosis Arterioscler Thromb Vasc Biol, October 1, 2000; 20(10): 2173 - 2174. [Full Text] [PDF]

				M Fluck, V Tunc-Civelek, and M Chiquet Rapid and reciprocal regulation of tenascin-C and tenascin-Y expression by loading of skeletal muscle J. Cell Sci., January 10, 2000; 113(20): 3583 - 3591. [Abstract] [PDF]

				R. T. Lee, C. Yamamoto, Y. Feng, S. Potter-Perigo, W. H. Briggs, K. T. Landschulz, T. G. Turi, J. F. Thompson, P. Libby, and T. N. Wight Mechanical Strain Induces Specific Changes in the Synthesis and Organization of Proteoglycans by Vascular Smooth Muscle Cells J. Biol. Chem., April 20, 2001; 276(17): 13847 - 13851. [Abstract] [Full Text] [PDF]

				D. Kessler, S. Dethlefsen, I. Haase, M. Plomann, F. Hirche, T. Krieg, and B. Eckes Fibroblasts in Mechanically Stressed Collagen Lattices Assume a "Synthetic" Phenotype J. Biol. Chem., September 21, 2001; 276(39): 36575 - 36585. [Abstract] [Full Text] [PDF]

				T. P. Quinn, M. Schlueter, S. J. Soifer, and J. A. Gutierrez Mechanotransduction in the Lung: Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells Am J Physiol Lung Cell Mol Physiol, May 1, 2002; 282(5): L897 - L903. [Abstract] [Full Text] [PDF]

				A. Y. Kim, P. L. Walinsky, F. D. Kolodgie, C. Bian, J. L. Sperry, C. B. Deming, E. A. Peck, J. G. Shake, G. B. Ang, R. H. Sohn, et al. Early Loss of Thrombomodulin Expression Impairs Vein Graft Thromboresistance: Implications for Vein Graft Failure Circ. Res., February 8, 2002; 90(2): 205 - 212. [Abstract] [Full Text] [PDF]