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• Iordache, F
• Buzila, C
• Constantinescu, A
• Andrei, E
• Maniu, H
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• Iordache, F
• Buzila, C
• Constantinescu, A
• Andrei, E
• Maniu, H
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• Iordache, F
• Buzila, C
• Constantinescu, A
• Andrei, E
• Maniu, H

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Int. J. Mol. Sci. 2012, 13(11), 15074-15085; doi:10.3390/ijms131115074

Article

Histone Deacetylase (HDAC) Inhibitors Down-Regulate Endothelial Lineage Commitment of Umbilical Cord Blood Derived Endothelial Progenitor Cells

Florin Iordache, Cosmin Buzila, Andrei Constantinescu, Eugen Andrei and Horia Maniu*

Institute of Cellular Biology and Pathology of Romanian Academy, “Nicolae Simionescu”, 8, B.P. Hasdeu, Bucharest 050568, Romania

* Author to whom correspondence should be addressed.

Received: 7 August 2012; in revised form: 18 October 2012 / Accepted: 8 November 2012 / Published: 15 November 2012

(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)

Download PDF Full-Text [605 KB, uploaded 15 November 2012 09:54 CET]

Abstract: 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.

Keywords: endothelial progenitor cells; differentiation; acetylation; histone deacetylases

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