PMID- 21763782
OWN - NLM
STAT- MEDLINE
DCOM- 20130501
LR  - 20211203
IS  - 1879-3649 (Electronic)
IS  - 1537-1891 (Linking)
VI  - 55
IP  - 5-6
DP  - 2011 Nov-Dec
TI  - Trichostatin A prevents neointimal hyperplasia via activation of Kruppel like 
      factor 4.
PG  - 127-34
LID - 10.1016/j.vph.2011.07.001 [doi]
AB  - The proliferation of vascular smooth muscle cells (VSMCs) is an integral part of 
      the mechanism of vascular diseases such as restenosis. Post-translational 
      modifications by histone deacetylase (HDAC) inhibitors play an important role in 
      the regulation of gene expression by inducing cell cycle arrest. However, the 
      role and mechanism of the HDAC inhibitor trichostatin A (TSA) on neointimal 
      proliferation remain unknown. In this study, we investigated the effect and 
      mechanism whereby TSA prevents the proliferation of VSMCs and neointimal 
      hyperplasia induced by balloon injury in rat carotid artery. Local administration 
      of TSA significantly prevented neointimal hyperplasia. TSA dramatically inhibited 
      the proliferation and DNA synthesis of VSMCs in response to FBS or PDGF-BB. 
      Overexpression of Kruppel like factor 4 (KLF4) blocked the cell proliferation and 
      DNA synthesis, as determined by the MTT and [(3)H]thymidine incorporation assays, 
      whereas knockdown of KLF4 resulted in an increase in VSMC proliferation. In 
      VSMCs, TSA increased the mRNA level and protein expression of KLF4. Treatment 
      with TSA or transfection of KLF4 increased the expression of both p21 and p27 and 
      promoter activity. In addition, the anti-proliferative activity of TSA was 
      recovered in KLF4-knockdown cells. These data demonstrate that TSA inhibits 
      neointimal thickening and VSMC proliferation via activation of the KLF4/p21/p27 
      signaling pathway.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Kee, Hae Jin
AU  - Kee HJ
AD  - Department of Pharmacology and Medical Research Center for Gene Regulation, 
      Chonnam National University Medical School, Gwangju 501-746, Republic of Korea. 
      sshjkee@empas.com
FAU - Kwon, Jin-Sook
AU  - Kwon JS
FAU - Shin, Sera
AU  - Shin S
FAU - Ahn, Youngkeun
AU  - Ahn Y
FAU - Jeong, Myung Ho
AU  - Jeong MH
FAU - Kook, Hyun
AU  - Kook H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110713
PL  - United States
TA  - Vascul Pharmacol
JT  - Vascular pharmacology
JID - 101130615
RN  - 0 (Cyclin-Dependent Kinase Inhibitor Proteins)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Klf4 protein, rat)
RN  - 0 (Kruppel-Like Factor 4)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Recombinant Proteins)
RN  - 3X2S926L3Z (trichostatin A)
SB  - IM
MH  - Animals
MH  - Aorta, Thoracic/cytology/drug effects/metabolism
MH  - Carotid Artery Diseases/*drug therapy/metabolism/pathology
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Cyclin-Dependent Kinase Inhibitor Proteins/antagonists & 
      inhibitors/genetics/metabolism
MH  - Gene Silencing
MH  - Histone Deacetylase Inhibitors/pharmacology/*therapeutic use
MH  - Hydroxamic Acids/pharmacology/*therapeutic use
MH  - Hyperplasia
MH  - Kruppel-Like Factor 4
MH  - Kruppel-Like Transcription Factors/antagonists & inhibitors/genetics/*metabolism
MH  - Male
MH  - Muscle, Smooth, Vascular/cytology/drug effects/metabolism
MH  - Promoter Regions, Genetic/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/antagonists & inhibitors/metabolism
MH  - Tunica Intima/*drug effects/metabolism/pathology
MH  - Up-Regulation/*drug effects
EDAT- 2011/07/19 06:00
MHDA- 2013/05/02 06:00
CRDT- 2011/07/19 06:00
PHST- 2011/01/10 00:00 [received]
PHST- 2011/06/28 00:00 [revised]
PHST- 2011/07/02 00:00 [accepted]
PHST- 2011/07/19 06:00 [entrez]
PHST- 2011/07/19 06:00 [pubmed]
PHST- 2013/05/02 06:00 [medline]
AID - S1537-1891(11)00067-X [pii]
AID - 10.1016/j.vph.2011.07.001 [doi]
PST - ppublish
SO  - Vascul Pharmacol. 2011 Nov-Dec;55(5-6):127-34. doi: 10.1016/j.vph.2011.07.001. 
      Epub 2011 Jul 13.