PMID- 15178640
OWN - NLM
STAT- MEDLINE
DCOM- 20041130
LR  - 20131121
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 95
IP  - 1
DP  - 2004 Jul 9
TI  - Myocyte enhancer factor 2 mediates vascular inflammation via the p38-dependent 
      pathway.
PG  - 42-9
AB  - Although it has been established that myocyte enhancer factor 2 (MEF2) plays 
      pivotal roles in the development of the cardiovascular system as well as skeletal 
      muscle cells, little is known of its role in vascular inflammatory diseases such 
      as atherosclerosis and restenosis after angioplasty. To investigate the role of 
      MEF2 in vascular inflammation and that of p38 in the activation of MEF2, we 
      infected cultured rat vascular smooth muscle cells (VSMCs) with an adenovirus 
      construct expressing a dominant-negative mutant of MEF2A (MEF2ASA) or 
      mitogen-activated protein kinase kinase 6 (MEK6AA), and examined their effects on 
      the expression of monocyte chemoattractant protein-1 (MCP-1), which is known to 
      play important roles in vascular inflammation. We also examined the role of MEF2 
      in vivo using a rat model of transluminal wire-induced injury of the femoral 
      artery. Angiotensin II (Ang II)-induced expression of MCP-1 mRNA was 
      significantly inhibited by infection with adenoviruses encoding MEF2ASA 
      (AdMEF2ASA) or MEK6AA. Ang II-induced increase of MCP-1 promoter activity was 
      also significantly suppressed by overexpression of MEF2ASA or MEK6AA. Ang II 
      stimulated the transactivating function of MEF2A and this activation was 
      inhibited by overexpression of MEK6AA. Infection with AdMEF2ASA suppressed MCP-1 
      expression in the femoral artery after the transluminal mechanical injury. 
      AdMEF2ASA infection also inhibited macrophages infiltration and neointimal 
      formation in the wire-injured femoral arteries. These results suggested that MEF2 
      activation via the p38-dependent pathway mediates vascular inflammation via 
      stimulation of MCP-1 expression in VSMCs and macrophages infiltration.
FAU - Suzuki, Etsu
AU  - Suzuki E
AD  - Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 
      Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. suzuki-2im@h.u-tokyo.ac.jp
FAU - Satonaka, Hiroshi
AU  - Satonaka H
FAU - Nishimatsu, Hiroaki
AU  - Nishimatsu H
FAU - Oba, Shigeyoshi
AU  - Oba S
FAU - Takeda, Ryo
AU  - Takeda R
FAU - Omata, Masao
AU  - Omata M
FAU - Fujita, Toshiro
AU  - Fujita T
FAU - Nagai, Ryozo
AU  - Nagai R
FAU - Hirata, Yasunobu
AU  - Hirata Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040603
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MEF2 Transcription Factors)
RN  - 0 (Myogenic Regulatory Factors)
RN  - 0 (Transcription Factors)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Arterial Occlusive Diseases/*etiology/immunology/pathology
MH  - Chemokine CCL2/metabolism
MH  - DNA-Binding Proteins/*physiology
MH  - Inflammation/etiology
MH  - MAP Kinase Signaling System
MH  - MEF2 Transcription Factors
MH  - Macrophages/immunology
MH  - Muscle, Smooth, Vascular/cytology/enzymology/*metabolism
MH  - Myogenic Regulatory Factors
MH  - Rats
MH  - Transcription Factors/*physiology
MH  - Transcriptional Activation
MH  - p38 Mitogen-Activated Protein Kinases/*physiology
EDAT- 2004/06/05 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/06/05 05:00
PHST- 2004/06/05 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/06/05 05:00 [entrez]
AID - 01.RES.0000134631.75684.4A [pii]
AID - 10.1161/01.RES.0000134631.75684.4A [doi]
PST - ppublish
SO  - Circ Res. 2004 Jul 9;95(1):42-9. doi: 10.1161/01.RES.0000134631.75684.4A. Epub 
      2004 Jun 3.