SEARCH:   Advanced

Blood, 1 June 2006, Vol. 107, No. 11, pp. 4354-4363. Prepublished online as a Blood First Edition Paper on February 2, 2006; DOI 10.1182/blood-2005-08-3465. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: 2005-08-3465v1 107/11/4354    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dekker, R. J Articles by Horrevoets, A. J Search for Related Content PubMed PubMed Citation Articles by Dekker, R. J Articles by Horrevoets, A. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 26, 2005 Accepted January 17, 2006 KLF2 provokes a gene expression pattern that establishes functional quiescent differentiation of the endothelium Rob J Dekker, Reinier A Boon, Mariska G Rondaij, Astrid Kragt, Oscar L Volger, Yvonne W Elderkamp, Joost C Meijers, Jan Voorberg, Hans Pannekoek, and Anton J Horrevoets* Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Sanquin Research and the Landsteiner Laboratory of the Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands * Corresponding author; email: a.j.horrevoets{at}amc.uva.nl. The flow-responsive transcription factor KLF2 is acquiring a leading role in the regulation of endothelial cell gene expression. A genome-wide micro-array expression profiling is described employing Lentivirus-mediated, 7-day overexpression of human KLF2 at levels observed under prolonged flow. KLF2 is not involved in lineage-typing as 42 endothelial-specific markers were unaffected. Rather, KLF2 generates a gene transcription profile ( >1000 genes) affecting key functional pathways such as cell migration, vasomotor function, inflammation and haemostasis, and induces a morphology change typical for shear exposure, including stress fiber formation. Protein levels for thrombomodulin, endothelial nitric oxide synthase and plasminogen activator inhibitor type-1 are altered to atheroprotective levels, even in the presence of the inflammatory cytokine TNF-. KLF2 attenuates cell migration by affecting multiple genes, including VEGFR2 and the potent anti-migratory SEMA3F. The distribution of Weibel-Palade bodies in cultured cell populations is normalized at the single cell level without interfering with their regulated, RalA-dependent release. In contrast, thrombin-induced release of Weibel-Palade bodies is significantly attenuated, consistent with the proposed role of vWF release at low-shear stress regions of the vasculature in atherosclerosis. These results establish that KLF2 acts as a central transcriptional switch point between the quiescent and activated states of the adult endothelial cell. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Kumar, T. A. Hoffman, J. DeRicco, A. Naqvi, M. K. Jain, and K. Irani Transcriptional repression of Kruppel like factor-2 by the adaptor protein p66shc FASEB J, December 1, 2009; 23(12): 4344 - 4352. [Abstract] [Full Text] [PDF] X. X. Wang, T. Jiang, Y. Shen, L. Adorini, M. Pruzanski, F. J. Gonzalez, P. Scherzer, L. Lewis, S. Miyazaki-Anzai, and M. Levi The farnesoid X receptor modulates renal lipid metabolism and diet-induced renal inflammation, fibrosis, and proteinuria Am J Physiol Renal Physiol, December 1, 2009; 297(6): F1587 - F1596. [Abstract] [Full Text] [PDF] F. Ali, M. Zakkar, K. Karu, E. A. Lidington, S. S. Hamdulay, J. J. Boyle, M. Zloh, A. Bauer, D. O. Haskard, P. C. Evans, et al. Induction of the Cytoprotective Enzyme Heme Oxygenase-1 by Statins Is Enhanced in Vascular Endothelium Exposed to Laminar Shear Stress and Impaired by Disturbed Flow J. Biol. Chem., July 10, 2009; 284(28): 18882 - 18892. [Abstract] [Full Text] [PDF] M. van den Biggelaar, E. A.M. Bouwens, N. A. Kootstra, R. P. Hebbel, J. Voorberg, and K. Mertens Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells Haematologica, May 1, 2009; 94(5): 670 - 678. [Abstract] [Full Text] [PDF] S. M. Meadows, M. C. Salanga, and P. A. Krieg Kruppel-like factor 2 cooperates with the ETS family protein ERG to activate Flk1 expression during vascular development Development, April 1, 2009; 136(7): 1115 - 1125. [Abstract] [Full Text] [PDF] P. J. Mack, Y. Zhang, S. Chung, V. Vickerman, R. D. Kamm, and G. Garcia-Cardena Biomechanical Regulation of Endothelium-dependent Events Critical for Adaptive Remodeling J. Biol. Chem., March 27, 2009; 284(13): 8412 - 8420. [Abstract] [Full Text] [PDF] R. De Caterina and R. Madonna Cytochromes CYP1A1 and CYP1B1: new pieces in the puzzle to understand the biomechanical paradigm of atherosclerosis Cardiovasc Res, March 1, 2009; 81(4): 629 - 632. [Full Text] [PDF] K. Sako, S. Fukuhara, T. Minami, T. Hamakubo, H. Song, T. Kodama, A. Fukamizu, J. S. Gutkind, G. Y. Koh, and N. Mochizuki Angiopoietin-1 Induces Kruppel-like Factor 2 Expression through a Phosphoinositide 3-Kinase/AKT-dependent Activation of Myocyte Enhancer Factor 2 J. Biol. Chem., February 27, 2009; 284(9): 5592 - 5601. [Abstract] [Full Text] [PDF] M. C. Meuwese, H. L. Mooij, M. Nieuwdorp, B. van Lith, R. Marck, H. Vink, J. J. P. Kastelein, and E. S. G. Stroes Partial recovery of the endothelial glycocalyx upon rosuvastatin therapy in patients with heterozygous familial hypercholesterolemia J. Lipid Res., January 1, 2009; 50(1): 148 - 153. [Abstract] [Full Text] [PDF] Q. Fu, J. Wang, M. Boerma, M. Berbee, X. Qiu, L. M. Fink, and M. Hauer-Jensen Involvement of Heat Shock Factor 1 in Statin-Induced Transcriptional Upregulation of Endothelial Thrombomodulin Circ. Res., August 15, 2008; 103(4): 369 - 377. [Abstract] [Full Text] [PDF] J. O. Fledderus, R. A. Boon, O. L. Volger, H. Hurttila, S. Yla-Herttuala, H. Pannekoek, A.-L. Levonen, and A. J.G. Horrevoets KLF2 Primes the Antioxidant Transcription Factor Nrf2 for Activation in Endothelial Cells Arterioscler Thromb Vasc Biol, July 1, 2008; 28(7): 1339 - 1346. [Abstract] [Full Text] [PDF] A. R. Kinderlerer, F. Ali, M. Johns, E. A. Lidington, V. Leung, J. J. Boyle, S. S. Hamdulay, P. C. Evans, D. O. Haskard, and J. C. Mason KLF2-dependent, Shear Stress-induced Expression of CD59: A NOVEL CYTOPROTECTIVE MECHANISM AGAINST COMPLEMENT-MEDIATED INJURY IN THE VASCULATURE J. Biol. Chem., May 23, 2008; 283(21): 14636 - 14644. [Abstract] [Full Text] [PDF] C. C. Matouk and P. A. Marsden Epigenetic Regulation of Vascular Endothelial Gene Expression Circ. Res., April 25, 2008; 102(8): 873 - 887. [Abstract] [Full Text] [PDF] T. T. Tuomisto, H. Lumivuori, E. Kansanen, S.-K. Hakkinen, M. P. Turunen, J. V. van Thienen, A. J. Horrevoets, A.-L. Levonen, and S. Yla-Herttuala Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an atheroprotective transcription factor, Kruppel-like factor 2 Cardiovasc Res, April 1, 2008; 78(1): 175 - 184. [Abstract] [Full Text] [PDF] J. Wu, C. S. Bohanan, J. C. Neumann, and J. B. Lingrel KLF2 Transcription Factor Modulates Blood Vessel Maturation through Smooth Muscle Cell Migration J. Biol. Chem., February 15, 2008; 283(7): 3942 - 3950. [Abstract] [Full Text] [PDF] R. D. Fontijn, O. L. Volger, J. O. Fledderus, A. Reijerkerk, H. E. de Vries, and A. J. G. Horrevoets SOX-18 controls endothelial-specific claudin-5 gene expression and barrier function Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H891 - H900. [Abstract] [Full Text] [PDF] G. Dai, S. Vaughn, Y. Zhang, E. T. Wang, G. Garcia-Cardena, and M. A. Gimbrone Jr Biomechanical Forces in Atherosclerosis-Resistant Vascular Regions Regulate Endothelial Redox Balance via Phosphoinositol 3-Kinase/Akt-Dependent Activation of Nrf2 Circ. Res., September 28, 2007; 101(7): 723 - 733. [Abstract] [Full Text] [PDF] J. C. Sluimer, N. Kisters, K. B. Cleutjens, O. L. Volger, A. J. Horrevoets, L. H. van den Akker, A.-P. J. Bijnens, and M. J. Daemen Dead or alive: gene expression profiles of advanced atherosclerotic plaques from autopsy and surgery Physiol Genomics, August 20, 2007; 30(3): 335 - 341. [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] K. L. Good and S. G. Tangye Decreased expression of Kruppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses PNAS, August 14, 2007; 104(33): 13420 - 13425. [Abstract] [Full Text] [PDF] O. L. Volger, J. O. Fledderus, N. Kisters, R. D. Fontijn, P. D. Moerland, J. Kuiper, T. J. van Berkel, A.-P. J.J. Bijnens, M. J.A.P. Daemen, H. Pannekoek, et al. Distinctive Expression of Chemokines and Transforming Growth Factor-{beta} Signaling in Human Arterial Endothelium during Atherosclerosis Am. J. Pathol., July 1, 2007; 171(1): 326 - 337. [Abstract] [Full Text] [PDF] G. B. Atkins and M. K. Jain Role of Kruppel-Like Transcription Factors in Endothelial Biology Circ. Res., June 22, 2007; 100(12): 1686 - 1695. [Abstract] [Full Text] [PDF] J. O. Fledderus, J. V. van Thienen, R. A. Boon, R. J. Dekker, J. Rohlena, O. L. Volger, A.-P. J. J. Bijnens, M. J. A. P. Daemen, J. Kuiper, T. J. C. van Berkel, et al. Prolonged shear stress and KLF2 suppress constitutive proinflammatory transcription through inhibition of ATF2 Blood, May 15, 2007; 109(10): 4249 - 4257. [Abstract] [Full Text] [PDF] R. A. Boon, J. O. Fledderus, O. L. Volger, E. J.A. van Wanrooij, E. Pardali, F. Weesie, J. Kuiper, H. Pannekoek, P. ten Dijke, and A. J.G. Horrevoets KLF2 Suppresses TGF-{beta} Signaling in Endothelium Through Induction of Smad7 and Inhibition of AP-1 Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 532 - 539. [Abstract] [Full Text] [PDF] T. Thum and J. Bauersachs Sports or statins for atheroprotection? New insight from Kruppel-like factor 2 Cardiovasc Res, November 1, 2006; 72(2): 193 - 195. [Full Text] [PDF] J. V. van Thienen, J. O. Fledderus, R. J. Dekker, J. Rohlena, G. A. van IJzendoorn, N. A. Kootstra, H. Pannekoek, and A. J.G. Horrevoets Shear stress sustains atheroprotective endothelial KLF2 expression more potently than statins through mRNA stabilization Cardiovasc Res, November 1, 2006; 72(2): 231 - 240. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020