PMID- 16960104
OWN - NLM
STAT- MEDLINE
DCOM- 20061113
LR  - 20220224
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 26
IP  - 11
DP  - 2006 Nov
TI  - Nonendothelial mesenchymal cell-derived MCP-1 is required for FGF-2-mediated 
      therapeutic neovascularization: critical role of the inflammatory/arteriogenic 
      pathway.
PG  - 2483-9
AB  - OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine that is 
      known as an inflammatory/arteriogenic factor. Angiogenesis contributes to the 
      inflammatory process; however, the molecular and cellular mechanisms of the links 
      among the inflammatory pathway, arteriogenesis, and angiogenesis have not been 
      well elucidated. METHODS AND RESULTS: Using murine models of fibroblast growth 
      factor-2 (FGF-2)-mediated therapeutic neovascularization, we here show that FGF-2 
      targets nonendothelial mesenchymal cells (NEMCs) enhancing both angiogenic 
      (vascular endothelial growth factor [VEGF]) and arteriogenic (MCP-1) signals via 
      independent signal transduction pathways. Severe hindlimb ischemia stimulated 
      MCP-1 expression that was strongly enhanced by FGF-2 gene transfer, and a 
      blockade of MCP-1 activity via a dominant negative mutant as well as a deficiency 
      of its functional receptor CCR2 resulted in the diminished recovery of blood flow 
      attributable to adaptive and therapeutic neovascularization. Tumor necrosis 
      factor (TNF)-alpha stimulated MCP-1 expression in all cell types tested, whereas 
      FGF-2-mediated upregulation of MCP-1 was found only in NEMCs but not in others, a 
      finding that was not affected by VEGF in vitro and in vivo. CONCLUSIONS: These 
      results indicate that FGF-2 targets NEMCs independently, enhancing both 
      angiogenic (VEGF) as well as inflammatory/arteriogenic (MCP-1) pathways. 
      Therefore, MCP-1/CCR2 plays a critical role in adaptive and FGF-2-mediated 
      therapeutic neovascularization.
FAU - Fujii, Takaaki
AU  - Fujii T
AD  - Division of Pathophysiological and Experimental Pathology, Department of 
      Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 
      Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
FAU - Yonemitsu, Yoshikazu
AU  - Yonemitsu Y
FAU - Onimaru, Mitsuho
AU  - Onimaru M
FAU - Tanii, Mitsugu
AU  - Tanii M
FAU - Nakano, Toshiaki
AU  - Nakano T
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Takehara, Takako
AU  - Takehara T
FAU - Inoue, Makoto
AU  - Inoue M
FAU - Hasegawa, Mamoru
AU  - Hasegawa M
FAU - Kuwano, Hiroyuki
AU  - Kuwano H
FAU - Sueishi, Katsuo
AU  - Sueishi K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060907
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adaptation, Physiological
MH  - Animals
MH  - Arteries/growth & development
MH  - Chemokine CCL2/*metabolism
MH  - Fibroblast Growth Factor 2/genetics/*metabolism
MH  - Gene Transfer Techniques
MH  - Hindlimb/blood supply
MH  - Inflammation Mediators/metabolism
MH  - Ischemia/metabolism/physiopathology
MH  - Male
MH  - Mesoderm/*cytology/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - *Neovascularization, Physiologic
MH  - Protein Kinase C/metabolism
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/metabolism
MH  - Regional Blood Flow
MH  - Signal Transduction
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2006/09/09 09:00
MHDA- 2006/11/14 09:00
CRDT- 2006/09/09 09:00
PHST- 2006/09/09 09:00 [pubmed]
PHST- 2006/11/14 09:00 [medline]
PHST- 2006/09/09 09:00 [entrez]
AID - 01.ATV.0000244684.23499.bf [pii]
AID - 10.1161/01.ATV.0000244684.23499.bf [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2483-9. doi: 
      10.1161/01.ATV.0000244684.23499.bf. Epub 2006 Sep 7.