Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1486K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rössig, L. Articles by Dimmeler, S. Search for Related Content PubMed PubMed Citation Articles by Rössig, L. Articles by Dimmeler, S. Related Collections Related Article Social Bookmarking                      What's this?

¹ Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, 60590 Frankfurt am Main, Germany
² Italian Foundation for Cancer Research, Institute of Molecular Oncology, 20146 Milan, Italy
³ Department of Biomolecular and Biotechnological Sciences, Faculty of Sciences, University of Milan, 20133 Milan, Italy

CORRESPONDENCE Stefanie Dimmeler: dimmeler{at}em.uni-frankfurt.de

The regulation of acetylation is central for the epigenetic control of lineage-specific gene expression and determines cell fate decisions. We provide evidence that the inhibition of histone deacetylases (HDACs) blocks the endothelial differentiation of adult progenitor cells. To define the mechanisms by which HDAC inhibition prevents endothelial differentiation, we determined the expression of homeobox transcription factors and demonstrated that HoxA9 expression is down-regulated by HDAC inhibitors. The causal involvement of HoxA9 in the endothelial differentiation of adult progenitor cells is supported by the finding that HoxA9 overexpression partially rescued the endothelial differentiation blockade induced by HDAC inhibitors. Knockdown and overexpression studies revealed that HoxA9 acts as a master switch to regulate the expression of prototypical endothelial-committed genes such as endothelial nitric oxide synthase, VEGF-R₂, and VE-cadherin, and mediates the shear stress–induced maturation of endothelial cells. Consistently, HoxA9-deficient mice exhibited lower numbers of endothelial progenitor cells and showed an impaired postnatal neovascularization capacity after the induction of ischemia. Thus, HoxA9 is regulated by HDACs and is critical for postnatal neovascularization.

L. Rössig, C. Urbich, and T. Brühl contributed equally to this work.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Article

Signaling commitment

Heather L. Van Epps
J. Exp. Med. 2005 201: 1691. [Full Text] [PDF]

This article has been cited by other articles:

• Obi, S., Yamamoto, K., Shimizu, N., Kumagaya, S., Masumura, T., Sokabe, T., Asahara, T., Ando, J. (2009). Fluid shear stress induces arterial differentiation of endothelial progenitor cells. J. Appl. Physiol. 106: 203-211 [Abstract] [Full Text]  
• Pirro, M., Bagaglia, F., Paoletti, L., Razzi, R., Mannarino, M. R. (2008). Review: Hypercholesterolemia-associated endothelial progenitor cell dysfunction. Ther Adv Cardiovasc Dis 2: 329-339 [Abstract]  
• Zhang, J., Burridge, K. A., Friedman, M. H. (2008). In vivo differences between endothelial transcriptional profiles of coronary and iliac arteries revealed by microarray analysis. Am. J. Physiol. Heart Circ. Physiol. 295: H1556-H1561 [Abstract] [Full Text]  
• Shen, W.-F., Hu, Y.-L., Uttarwar, L., Passegue, E., Largman, C. (2008). MicroRNA-126 Regulates HOXA9 by Binding to the Homeobox. Mol. Cell. Biol. 28: 4609-4619 [Abstract] [Full Text]  
• Zampetaki, A., Kirton, J. P., Xu, Q. (2008). Vascular repair by endothelial progenitor cells. Cardiovasc Res 78: 413-421 [Abstract] [Full Text]  
• Xu, Q. (2008). Stem Cells and Transplant Arteriosclerosis. Circ. Res. 102: 1011-1024 [Abstract] [Full Text]  
• Tongers, J., Knapp, J.-M., Korf, M., Kempf, T., Limbourg, A., Limbourg, F. P., Li, Z., Fraccarollo, D., Bauersachs, J., Han, X., Drexler, H., Fiedler, B., Wollert, K. C. (2008). Haeme oxygenase promotes progenitor cell mobilization, neovascularization, and functional recovery after critical hindlimb ischaemia in mice. Cardiovasc Res 78: 294-300 [Abstract] [Full Text]  
• Matouk, C. C., Marsden, P. A. (2008). Epigenetic Regulation of Vascular Endothelial Gene Expression. Circ. Res. 102: 873-887 [Abstract] [Full Text]  
• Illi, B., Russo, C. D., Colussi, C., Rosati, J., Pallaoro, M., Spallotta, F., Rotili, D., Valente, S., Ragone, G., Martelli, F., Biglioli, P., Steinkuhler, C., Gallinari, P., Mai, A., Capogrossi, M. C., Gaetano, C. (2008). Nitric Oxide Modulates Chromatin Folding in Human Endothelial Cells via Protein Phosphatase 2A Activation and Class II Histone Deacetylases Nuclear Shuttling. Circ. Res. 102: 51-58 [Abstract] [Full Text]  
• Potente, M., Ghaeni, L., Baldessari, D., Mostoslavsky, R., Rossig, L., Dequiedt, F., Haendeler, J., Mione, M., Dejana, E., Alt, F. W., Zeiher, A. M., Dimmeler, S. (2007). SIRT1 controls endothelial angiogenic functions during vascular growth. Genes Dev. 21: 2644-2658 [Abstract] [Full Text]  
• Bandyopadhyay, S., Ashraf, M. Z., Daher, P., Howe, P. H., DiCorleto, P. E. (2007). HOXA9 Participates in the Transcriptional Activation of E-Selectin in Endothelial Cells. Mol. Cell. Biol. 27: 4207-4216 [Abstract] [Full Text]  
• Hu, Y.-L., Passegue, E., Fong, S., Largman, C., Lawrence, H. J. (2007). Evidence that the Pim1 kinase gene is a direct target of HOXA9. Blood 109: 4732-4738 [Abstract] [Full Text]  
• Hassan, M. Q., Tare, R., Lee, S. H., Mandeville, M., Weiner, B., Montecino, M., van Wijnen, A. J., Stein, J. L., Stein, G. S., Lian, J. B. (2007). HOXA10 Controls Osteoblastogenesis by Directly Activating Bone Regulatory and Phenotypic Genes. Mol. Cell. Biol. 27: 3337-3352 [Abstract] [Full Text]  
• Diehl, F., Rossig, L., Zeiher, A. M., Dimmeler, S., Urbich, C. (2007). The histone methyltransferase MLL is an upstream regulator of endothelial-cell sprout formation. Blood 109: 1472-1478 [Abstract] [Full Text]  
• Fiskus, W., Pranpat, M., Balasis, M., Herger, B., Rao, R., Chinnaiyan, A., Atadja, P., Bhalla, K. (2006). Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells. Molecular Cancer Therapeutics 5: 3096-3104 [Abstract] [Full Text]  
• Xiao, Q., Zeng, L., Zhang, Z., Margariti, A., Ali, Z. A, Channon, K. M., Xu, Q., Hu, Y. (2006). Sca-1+ Progenitors Derived From Embryonic Stem Cells Differentiate Into Endothelial Cells Capable of Vascular Repair After Arterial Injury. Arterioscler. Thromb. Vasc. Bio. 26: 2244-2251 [Abstract] [Full Text]  
• Zeng, L., Xiao, Q., Margariti, A., Zhang, Z., Zampetaki, A., Patel, S., Capogrossi, M. C., Hu, Y., Xu, Q. (2006). HDAC3 is crucial in shear- and VEGF-induced stem cell differentiation toward endothelial cells. JCB 174: 1059-1069 [Abstract] [Full Text]  
• Marumo, T., Uchimura, H., Hayashi, M., Hishikawa, K., Fujita, T. (2006). Aldosterone Impairs Bone Marrow-Derived Progenitor Cell Formation. Hypertension 48: 490-496 [Abstract] [Full Text]  
• de Boer, H.C., Verseyden, C., Ulfman, L.H., Zwaginga, J.J., Bot, I., Biessen, E.A., Rabelink, T.J., van Zonneveld, A.J. (2006). Fibrin and Activated Platelets Cooperatively Guide Stem Cells to a Vascular Injury and Promote Differentiation Towards an Endothelial Cell Phenotype. Arterioscler. Thromb. Vasc. Bio. 26: 1653-1659 [Abstract] [Full Text]  
• Daftary, G. S., Taylor, H. S. (2006). Endocrine Regulation of HOX Genes. Endocr. Rev. 27: 331-355 [Abstract] [Full Text]  
• Mohri, T., Fujio, Y., Maeda, M., Ito, T., Iwakura, T., Oshima, Y., Uozumi, Y., Segawa, M., Yamamoto, H., Kishimoto, T., Azuma, J. (2006). Leukemia Inhibitory Factor Induces Endothelial Differentiation in Cardiac Stem Cells. J. Biol. Chem. 281: 6442-6447 [Abstract] [Full Text]  
• Qian, D. Z., Kato, Y., Shabbeer, S., Wei, Y., Verheul, H. M.W., Salumbides, B., Sanni, T., Atadja, P., Pili, R. (2006). Targeting Tumor Angiogenesis with Histone Deacetylase Inhibitors: the Hydroxamic Acid Derivative LBH589. Clin. Cancer Res. 12: 634-642 [Abstract] [Full Text]  
• Rossig, L., Urbich, C., Bruhl, T., Dernbach, E., Heeschen, C., Chavakis, E., Sasaki, K.-i., Aicher, D., Diehl, F., Seeger, F., Potente, M., Aicher, A., Zanetta, L., Dejana, E., Zeiher, A. M., Dimmeler, S. (2005). Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells. JCB 169: i13-i13 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS