PMID- 20428211
OWN - NLM
STAT- MEDLINE
DCOM- 20110119
LR  - 20211025
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 17
IP  - 9
DP  - 2010 Sep
TI  - Ets-1 promotes the progression of cerebral aneurysm by inducing the expression of 
      MCP-1 in vascular smooth muscle cells.
PG  - 1117-23
LID - 10.1038/gt.2010.60 [doi]
AB  - Cerebral aneurysm (CA) rupture is one of the leading causes of stroke death. 
      Recent experimental studies suggest that the pathophysiology of CA is closely 
      associated with inflammation. A transcription factor, Ets-1, has been shown to 
      regulate vascular inflammation and remodeling in a physiological and pathological 
      condition. The expression and role of Ets-1 in CA development has been 
      investigated in this study. Ets-1 was expressed and activated mainly in vascular 
      smooth muscle cells (VSMCs) in both experimentally induced rat CAs and human CA 
      walls by immunohistochemistry, western blotting and enzyme-linked mobility shift 
      assay. The downstream target of Ets-1 in CA development was identified by 
      chromatin immunoprecipitation (CHIP) analysis. CHIP analysis revealed that Ets-1 
      transactivated monocyte chemoattractant protein-1 (MCP-1) expression in CA walls. 
      Treatment with ets decoy oligodeoxynucleotides resulted in the prevention of CA 
      enlargement, upregulation of MCP-1 expression and increase in macrophage 
      accumulation in CA walls. In conclusion, Ets-1 mediates MCP-1 expression in VSMCs 
      in CA walls, thus promoting the progression of CAs. Inhibition of DNA-binding 
      activity of Ets-1 may lead to the prevention of human CA enlargement and rupture. 
      Results of this study will provide us a clue to a novel therapeutic strategy for 
      CAs.
FAU - Aoki, T
AU  - Aoki T
AD  - Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, 
      Japan.
FAU - Kataoka, H
AU  - Kataoka H
FAU - Nishimura, M
AU  - Nishimura M
FAU - Ishibashi, R
AU  - Ishibashi R
FAU - Morishita, R
AU  - Morishita R
FAU - Miyamoto, S
AU  - Miyamoto S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100429
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Chemokine CCL2)
RN  - 0 (Proto-Oncogene Protein c-ets-1)
SB  - IM
EIN - Gene Ther. 2013 Feb;20(2):235
MH  - Animals
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Chromatin Immunoprecipitation
MH  - Humans
MH  - Immunohistochemistry
MH  - Intracranial Aneurysm/*etiology/metabolism/pathology
MH  - Male
MH  - Muscle, Smooth, Vascular/cytology/*metabolism
MH  - Myocytes, Smooth Muscle/cytology/*metabolism
MH  - Proto-Oncogene Protein c-ets-1/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2010/04/30 06:00
MHDA- 2011/01/20 06:00
CRDT- 2010/04/30 06:00
PHST- 2010/04/30 06:00 [entrez]
PHST- 2010/04/30 06:00 [pubmed]
PHST- 2011/01/20 06:00 [medline]
AID - gt201060 [pii]
AID - 10.1038/gt.2010.60 [doi]
PST - ppublish
SO  - Gene Ther. 2010 Sep;17(9):1117-23. doi: 10.1038/gt.2010.60. Epub 2010 Apr 29.