PMID- 15284091
OWN - NLM
STAT- MEDLINE
DCOM- 20050324
LR  - 20121115
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 24
IP  - 10
DP  - 2004 Oct
TI  - Antimonocyte chemoattractant protein-1 gene therapy attenuates graft 
      vasculopathy.
PG  - 1886-90
AB  - OBJECTIVE: Accelerated coronary arteriosclerosis remains a major problem in the 
      long-term survival of cardiac transplant recipients. However, the pathogenesis of 
      graft vasculopathy is poorly understood, and there is no effective therapy. 
      Transplant arteriosclerosis is characterized by early mononuclear cell attachment 
      on the transplanted vessel followed by development of concentric neointimal 
      hyperplasia. Early and persistent expression of monocyte chemoattractant 
      protein-1 (MCP-1) in cardiac allografts has been implicated for the pathogenesis 
      of transplant arteriosclerosis. METHODS AND RESULTS: We investigated whether 
      anti-MCP-1 gene therapy can inhibit the development of intima hyperplasia in a 
      mouse model of cardiac transplantation. Either the dominant-negative form of 
      MCP-1 (7ND) or control vector was transfected into the skeletal muscles of B10.D2 
      mice. Cardiac allografts from DBA/2 mice were transplanted heterotopically into 
      B10.D2 mice. 7ND gene transfer was associated with a significant reduction of the 
      number of mononuclear cells accumulating in the lumen of the graft coronary 
      arteries at 1 week and an attenuation of the development of the lesion at 8 weeks 
      (intima/media ratio 0.79+/-0.05 versus 0.48+/-0.04). CONCLUSIONS: The 
      MCP-1/chemokine receptor 2 (CCR2) signaling pathway plays a critical role in the 
      pathogenesis of graft vasculopathy. This new anti-MCP-1 gene therapy might be 
      useful to treat graft vascular disease.
FAU - Saiura, Akio
AU  - Saiura A
AD  - Department of Surgery, University of Tokyo, Graduate School of Medicine, Japan.
FAU - Sata, Masataka
AU  - Sata M
FAU - Hiasa, Ken-ichi
AU  - Hiasa K
FAU - Kitamoto, Shiro
AU  - Kitamoto S
FAU - Washida, Miwa
AU  - Washida M
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Nagai, Ryozo
AU  - Nagai R
FAU - Makuuchi, Masatoshi
AU  - Makuuchi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040729
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 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Animals
MH  - Arteriosclerosis/*prevention & control
MH  - Chemokine CCL2/biosynthesis/*genetics
MH  - Coronary Vessels/physiology
MH  - Disease Models, Animal
MH  - Gene Transfer Techniques
MH  - Genes, Dominant/physiology
MH  - Genetic Therapy/*methods
MH  - Heart Transplantation/methods
MH  - Hyperplasia/prevention & control
MH  - Inflammation/genetics/pathology
MH  - Leukocytes, Mononuclear/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Mice, Inbred Strains
MH  - Muscle, Skeletal/chemistry/metabolism
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/metabolism
MH  - Signal Transduction/genetics
MH  - Transplantation, Heterotopic
MH  - Transplantation, Homologous
MH  - Tunica Intima/pathology
EDAT- 2004/07/31 05:00
MHDA- 2005/03/25 09:00
CRDT- 2004/07/31 05:00
PHST- 2004/07/31 05:00 [pubmed]
PHST- 2005/03/25 09:00 [medline]
PHST- 2004/07/31 05:00 [entrez]
AID - 01.ATV.0000141045.49616.6f [pii]
AID - 10.1161/01.ATV.0000141045.49616.6f [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):1886-90. doi: 
      10.1161/01.ATV.0000141045.49616.6f. Epub 2004 Jul 29.