title: Histone deacetylase (HDAC) inhibitors down-regulate endothelial lineage commitment of umbilical cord blood derived endothelial progenitor cells.
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 VEGFR(2)) 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 VEGFR(2), 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.
authors.affiliation: Institute of Cellular Biology and Pathology of Romanian Academy, "Nicolae Simionescu",  8, B.P. Hasdeu, Bucharest 050568, Romania. horia.maniu@icbp.ro.
authors.forename: Florin
authors.initials: F
authors.lastname: Iordache
authors.forename: Cosmin
authors.initials: C
authors.lastname: Buzila
authors.forename: Andrei
authors.initials: A
authors.lastname: Constantinescu
authors.forename: Eugen
authors.initials: E
authors.lastname: Andrei
authors.forename: Horia
authors.initials: H
authors.lastname: Maniu
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D066026:Endothelial Progenitor Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D019098:Telomerase / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D019098:Telomerase