PMID- 12065319
OWN - NLM
STAT- MEDLINE
DCOM- 20020620
LR  - 20190706
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 90
IP  - 11
DP  - 2002 Jun 14
TI  - Importance of monocyte chemoattractant protein-1 pathway in neointimal 
      hyperplasia after periarterial injury in mice and monkeys.
PG  - 1167-72
AB  - Neointimal hyperplasia is a major cause of restenosis after coronary 
      intervention. Because vascular injury is now recognized to involve an 
      inflammatory response, monocyte chemoattractant protein-1 (MCP-1) might be 
      involved in underlying mechanisms of restenosis. In the present study, we 
      demonstrate the important role of MCP-1 in neointimal hyperplasia after 
      cuff-induced arterial injury. In the first set of experiments, placement of a 
      nonconstricting cuff around the femoral artery of intact mice and monkeys 
      resulted in inflammation in the early stages and subsequent neointimal 
      hyperplasia at the late stages. We transfected with an N-terminal deletion mutant 
      of the human MCP-1 gene into skeletal muscles to block MCP-1 activity in vivo. 
      This mutant MCP-1 works as a dominant-negative inhibitor of MCP-1. This strategy 
      inhibited early vascular inflammation (monocyte infiltration, increased 
      expression of MCP-1, and inflammatory cytokines) and late neointimal hyperplasia. 
      In the second set of experiments, the cuff-induced neointimal hyperplasia was 
      found to be less in CCR2-deficient mice than in control CCR2(+/+) mice. The 
      MCP-1/CCR2 pathway plays a central role in the pathogenesis of neointimal 
      hyperplasia in cuffed femoral artery of mice and monkeys. Therefore, the 
      MCP-1/CCR2 pathway can be a therapeutic target for human restenosis after 
      coronary intervention.
FAU - Egashira, Kensuke
AU  - Egashira K
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University, Fukuoka, Japan. egashira@cardiol.med.kyushu-u.ac.jp
FAU - Zhao, Qingwei
AU  - Zhao Q
FAU - Kataoka, Chu
AU  - Kataoka C
FAU - Ohtani, Kishou
AU  - Ohtani K
FAU - Usui, Makoto
AU  - Usui M
FAU - Charo, Israel F
AU  - Charo IF
FAU - Nishida, Ken-Ichi
AU  - Nishida K
FAU - Inoue, Shujiro
AU  - Inoue S
FAU - Katoh, Makoto
AU  - Katoh M
FAU - Ichiki, Toshihiro
AU  - Ichiki T
FAU - Takeshita, Akira
AU  - Takeshita A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (CCR2 protein, human)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/blood/genetics/*physiology
MH  - Femoral Artery/*injuries/pathology
MH  - Gene Expression
MH  - Genotype
MH  - Humans
MH  - Hyperplasia
MH  - Immunohistochemistry
MH  - Macaca fascicularis
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Plasmids/genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics/metabolism
MH  - Signal Transduction
MH  - Time Factors
MH  - Transfection
MH  - Tunica Intima/metabolism/*pathology
EDAT- 2002/06/18 10:00
MHDA- 2002/06/21 10:01
CRDT- 2002/06/18 10:00
PHST- 2002/06/18 10:00 [pubmed]
PHST- 2002/06/21 10:01 [medline]
PHST- 2002/06/18 10:00 [entrez]
AID - 10.1161/01.res.0000020561.03244.7e [doi]
PST - ppublish
SO  - Circ Res. 2002 Jun 14;90(11):1167-72. doi: 10.1161/01.res.0000020561.03244.7e.