PMID- 14500291
OWN - NLM
STAT- MEDLINE
DCOM- 20040406
LR  - 20220331
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 23
IP  - 11
DP  - 2003 Nov 1
TI  - Molecular mechanism and role of endothelial monocyte chemoattractant protein-1 
      induction by vascular endothelial growth factor.
PG  - 1996-2001
AB  - OBJECTIVE: We investigated the role of monocyte chemoattractant protein-1 (MCP-1) 
      in vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular 
      permeability and the underlying molecular mechanism of VEGF-induced endothelial 
      MCP-1 expression in vitro and in vivo. METHODS AND RESULTS: We used an anti-MCP-1 
      neutralizing antibody for specific inhibition of MCP-1. VEGF increased tubule 
      formation in the angiogenesis assay and vascular permeability in the Miles assay, 
      and these effects were markedly inhibited by anti-MCP-1 antibody. Using a 
      luciferase MCP-1 promoter-gene assay, we found that the activator protein-1 
      (AP-1) binding site of the MCP-1 promoter region contributes to the increase in 
      MCP-1 promoter activity by VEGF. To specifically inhibit AP-1, we used 
      recombinant adenovirus containing a dominant-negative c-Jun (Ad-DN-c-Jun). 
      Ad-DN-c-Jun inhibited VEGF-induced endothelial MCP-1 mRNA expression and promoter 
      activity in vitro. In vivo gene transfer of DN-c-Jun into rat carotid artery, 
      with the hemagglutinating virus of the Japan liposome method, significantly 
      blocked VEGF-induced MCP-1 and macrophage/monocyte (ED1) expression in 
      endothelium. CONCLUSIONS: These results reveal that endothelial MCP-1 induced by 
      VEGF seems to participate in angiogenesis, vascular leakage, or arteriosclerosis. 
      AP-1 plays a critical role in the molecular mechanism underlying induction of 
      MCP-1 by VEGF.
FAU - Yamada, Motoko
AU  - Yamada M
AD  - Department of Pharmacology, Osaka City University Medical School, Abeno, Osaka, 
      Japan.
FAU - Kim, Shokei
AU  - Kim S
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Takeya, Motohiro
AU  - Takeya M
FAU - Ikeda, Tomohiro
AU  - Ikeda T
FAU - Mimura, Osamu
AU  - Mimura O
FAU - Iwao, Hiroshi
AU  - Iwao H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030918
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Animals
MH  - Capillary Permeability/*physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/antagonists & inhibitors/genetics/immunology/*metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Endothelial Cells/*metabolism
MH  - Gene Expression
MH  - Genes, jun/genetics
MH  - Male
MH  - Neovascularization, Physiologic/*physiology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transcription Factor AP-1/*genetics
MH  - Transcription, Genetic
MH  - Vascular Endothelial Growth Factor A/*metabolism
EDAT- 2003/09/23 05:00
MHDA- 2004/04/07 05:00
CRDT- 2003/09/23 05:00
PHST- 2003/09/23 05:00 [pubmed]
PHST- 2004/04/07 05:00 [medline]
PHST- 2003/09/23 05:00 [entrez]
AID - 01.ATV.0000096208.80992.63 [pii]
AID - 10.1161/01.ATV.0000096208.80992.63 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2003 Nov 1;23(11):1996-2001. doi: 
      10.1161/01.ATV.0000096208.80992.63. Epub 2003 Sep 18.