{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:13:03Z","timestamp":1779909183016,"version":"3.53.1"},"reference-count":34,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2012,11,15]],"date-time":"2012-11-15T00:00:00Z","timestamp":1352937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>To test the involvement of histone deacetylases (HDACs) activity in endothelial lineage progression, we investigated the effects of HDAC inhibitors on endothelial progenitors cells (EPCs) derived from umbilical cord blood (UCB). Adherent EPCs, that expressed the endothelial marker proteins (PCAM-1, CD105, CD133, and VEGFR2) revealed by flow cytometry were treated with three HDAC inhibitors: Butyrate (BuA), Trichostatin A (TSA), and Valproic acid (VPA). RT-PCR assay showed that HDAC inhibitors down-regulated the expression of endothelial genes such as VE-cadherin, CD133, CXCR4 and Tie-2. Furthermore, flow cytometry analysis illustrated that HDAC inhibitors selectively reduce the expression of VEGFR2, CD117, VE-cadherin, and ICAM-1, whereas the expression of CD34 and CD45 remained unchanged, demonstrating that HDAC is involved in endothelial differentiation of progenitor cells. Real-Time PCR demonstrated that TSA down-regulated telomerase activity probably via suppression of hTERT expression, suggesting that HDAC inhibitor decreased cell proliferation. Cell motility was also decreased after treatment with HDAC inhibitors as shown by wound-healing assay. The balance of acethylation\/deacethylation kept in control by the activity of HAT (histone acetyltransferases)\/HDAC enzymes play an important role in differentiation of stem cells by regulating proliferation and endothelial lineage commitment.<\/jats:p>","DOI":"10.3390\/ijms131115074","type":"journal-article","created":{"date-parts":[[2012,11,15]],"date-time":"2012-11-15T11:03:44Z","timestamp":1352977424000},"page":"15074-15085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Histone Deacetylase (HDAC) Inhibitors Down-Regulate Endothelial Lineage Commitment of Umbilical Cord Blood Derived Endothelial Progenitor Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Florin","family":"Iordache","sequence":"first","affiliation":[{"name":"Institute of Cellular Biology and Pathology of Romanian Academy, \u201cNicolae Simionescu\u201d, 8, B.P. Hasdeu, Bucharest 050568, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosmin","family":"Buzila","sequence":"additional","affiliation":[{"name":"Institute of Cellular Biology and Pathology of Romanian Academy, \u201cNicolae Simionescu\u201d, 8, B.P. Hasdeu, Bucharest 050568, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Constantinescu","sequence":"additional","affiliation":[{"name":"Institute of Cellular Biology and Pathology of Romanian Academy, \u201cNicolae Simionescu\u201d, 8, B.P. Hasdeu, Bucharest 050568, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Andrei","sequence":"additional","affiliation":[{"name":"Institute of Cellular Biology and Pathology of Romanian Academy, \u201cNicolae Simionescu\u201d, 8, B.P. Hasdeu, Bucharest 050568, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horia","family":"Maniu","sequence":"additional","affiliation":[{"name":"Institute of Cellular Biology and Pathology of Romanian Academy, \u201cNicolae Simionescu\u201d, 8, B.P. Hasdeu, Bucharest 050568, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2012,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1126\/science.1063127","article-title":"Translating the Histone Code","volume":"293","author":"Jenuwein","year":"2001","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2007.01.015","article-title":"The Role of Chromatin during Transcription","volume":"128","author":"Li","year":"2007","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.cell.2010.08.011","article-title":"The Language of Histone Crosstalk","volume":"142","author":"Lee","year":"2010","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.diff.2009.07.002","article-title":"Epigenetics, stem cells and epithelial cell fate","volume":"78","author":"Vincent","year":"2009","journal-title":"Differentiation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrg1655","article-title":"DNA methylation and human disease","volume":"6","author":"Robertson","year":"2005","journal-title":"Nat. Rev. Genet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1146\/annurev.physiol.010908.163145","article-title":"Stem cells, self-renewal, and differentiation in the intestinal epithelium","volume":"71","author":"Flier","year":"2009","journal-title":"Annu. Rev. Physiol"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"16467","DOI":"10.1074\/jbc.M412960200","article-title":"Role of Histone Deacetylation in Cell-specific Expression of Endothelial Nitric-oxide Synthase","volume":"280","author":"Gan","year":"2005","journal-title":"J. Biol. Chem"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4161\/epi.3.1.5736","article-title":"HDACs and HDAC inhibitors in colon cancer","volume":"3","author":"Mariadason","year":"2008","journal-title":"Epigenetics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.canlet.2008.08.016","article-title":"HDAC family: What are the cancer relevant targets?","volume":"277","author":"Witt","year":"2009","journal-title":"Cancer Lett"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Monneret, C. (2005). Histone deacetylase inhibitors. Eur. J. Med. Chem., 401\u2013413.","DOI":"10.1002\/chin.200519250"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1159\/000331714","article-title":"Integration Properties of Wharton\u2019s Jelly-derived Novel Mesenchymal Stem Cells into Ventricular Slices of Murine Hearts","volume":"28","author":"Lupu","year":"2011","journal-title":"Cell. Physiol. Biochem"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1111\/j.1582-4934.2010.01197.x","article-title":"Direct Contact of Umbilical Cord Blood Endothelial Progenitors with Living Cardiac Tissue is a Requirement for Vascular Tube-like Structures Formation","volume":"15","author":"Lupu","year":"2011","journal-title":"J. Cell. Mol. Med"},{"key":"ref_13","first-page":"330","article-title":"Effects of plant lectin and extracts on adhesion molecules of endothelial progenitors","volume":"6","author":"Iordache","year":"2011","journal-title":"Cent. Eur. J. Biol"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1126\/science.275.5302.964","article-title":"Isolation of putative progenitor endothelial cells for angiogenesis","volume":"275","author":"Asahara","year":"1997","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0609.2005.00579.x","article-title":"Transplantation of umbilical cord blood derived endothelial progenitor cells: A promising method of therapeutic revascularisation","volume":"76","author":"Zhang","year":"2006","journal-title":"Eur. J. Haematol"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30673","DOI":"10.1074\/jbc.M109.042242","article-title":"Expression levels of histone deacetylases determine the cell fate of hematopoietic progenitors","volume":"284","author":"Wada","year":"2009","journal-title":"J. Biol. Chem"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/cvr\/cvr019","article-title":"Epigenetic regulation of cardiovascular differentiation","volume":"90","author":"Ohtani","year":"2011","journal-title":"Cardiovasc. Res"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1161\/01.HYP.0000168923.92885.f7","article-title":"Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases","volume":"46","author":"Dzau","year":"2005","journal-title":"Hypertension"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.biochi.2007.07.011","article-title":"Targeting telomeres and telomerase","volume":"90","author":"Cian","year":"2008","journal-title":"Biochimie"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1161\/01.CIR.0000027584.85865.B4","article-title":"Constitutive human telomerase reverse transcriptase expression enhances regenerative properties of endothelial progenitor cells","volume":"106","author":"Murasawa","year":"2002","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"26141","DOI":"10.1074\/jbc.274.37.26141","article-title":"Human endothelial cell life extension by telomerase expression","volume":"274","author":"Yang","year":"1999","journal-title":"J. Biol. Chem"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1538-7836.2009.03407.x","article-title":"Defining human endothelial progenitor cells","volume":"7","author":"Yoder","year":"2009","journal-title":"J. Thromb. Haemost"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/nprot.2007.111","article-title":"A protocol for phenotypic detection and enumeration of circulating endothelial cells and circulating progenitor cells in human blood","volume":"2","author":"Duda","year":"2007","journal-title":"Nat. Protocol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1084\/jem.20042097","article-title":"Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells","volume":"201","author":"Urbich","year":"2005","journal-title":"J. Exp. Med"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1126\/science.1120140","article-title":"Stem Cell Self-Renewal Controlled by Chromatin Remodeling Factors","volume":"310","author":"Xi","year":"2005","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kretsovali, A., Hadjimichael, C., and Charmpilas, N. (2012). Histone Deacetylase Inhibitors in Cell Pluripotency, Differentiation, and Reprogramming. Stem Cells Int.","DOI":"10.1155\/2012\/184154"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.1002\/jcp.22679","article-title":"The regulatory role of histone deacetylase inhibitors in Fgf4 expression is dependent on the differentiation state of pluripotent stem cells","volume":"226","author":"Shi","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e22158","DOI":"10.1371\/journal.pone.0022158","article-title":"Histone Deacetylase Inhibition Enhances Self Renewal and Cardioprotection by Human Cord Blood-Derived CD34+ Cells","volume":"6","author":"Burba","year":"2011","journal-title":"PLoS One"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1161\/CIRCRESAHA.107.149377","article-title":"Histone deacetylase 7 silencing alters endothelial cell migration, a key step in angiogenesis","volume":"101","author":"Mottet","year":"2007","journal-title":"Circ. Res"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/gene.10250","article-title":"Histone deacetylase activity is required for embryonic stem cell differentiation","volume":"38","author":"Lee","year":"2004","journal-title":"Genesis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1093\/emboj\/21.11.2672","article-title":"Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression","volume":"21","author":"Lagger","year":"2002","journal-title":"EMBO J"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/sj.onc.1205108","article-title":"Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling","volume":"21","author":"Deroanne","year":"2002","journal-title":"Oncogene"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1161\/CIRCRESAHA.107.171025","article-title":"Epigenetic Regulation of Vascular Endothelial Gene Expression","volume":"102","author":"Matouk","year":"2008","journal-title":"Circ. Res"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nature05772","article-title":"Recovery of learning and memory is associated with chromatin remodelling","volume":"447","author":"Fischer","year":"2007","journal-title":"Nature"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/13\/11\/15074\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:53:35Z","timestamp":1760219615000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/13\/11\/15074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,15]]},"references-count":34,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2012,11]]}},"alternative-id":["ijms131115074"],"URL":"https:\/\/doi.org\/10.3390\/ijms131115074","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,15]]}}}