PMID- 17126840
OWN - NLM
STAT- MEDLINE
DCOM- 20071227
LR  - 20121115
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 194
IP  - 2
DP  - 2007 Oct
TI  - Catheter-based adenovirus-mediated anti-monocyte chemoattractant gene therapy 
      attenuates in-stent neointima formation in cynomolgus monkeys.
PG  - 309-16
AB  - We have previously demonstrated great benefit from anti-monocyte chemoattractant 
      protein-1 (MCP-1) gene therapy by "systemic" transfer of an N-terminal deletion 
      mutant of human MCP-1 (called 7ND) gene into skeletal muscle for treatment of 
      restenosis and atherosclerosis. However, recent evidence suggests that "local" 
      gene transfer may be a clinically relevant approach. We therefore tested the 
      hypothesis that catheter-based adenovirus-mediated anti-MCP-1 gene therapy 
      attenuates stent-associated neointima formation. Bare metal stents were implanted 
      in iliac arteries of cynomolgus monkeys fed a high cholesterol diet. Immediately 
      after the stenting procedure, normal saline or recombinant adenoviral vector 
      containing LacZ or the 7ND gene was administered locally into the stenting site 
      through a Remedy channel-delivery catheter. Compared to saline infusion or LacZ 
      gene transfer, 7ND gene transfer markedly reduced inflammatory changes at an 
      early stage and attenuated neointima formation after 4 weeks. This strategy also 
      reduced the increased production of pro-inflammatory and growth-promoting factors 
      such platelet-derived growth factor. No systemic adverse effects of 7ND gene 
      transfer were detected. There were no significant differences in serum 
      cholesterol levels among the three groups. These data suggest that catheter-based 
      adenovirus-mediated anti-MCP-1 gene therapy may be a clinically relevant and 
      feasible strategy for treatment of in-stent restenosis.
FAU - Nakano, Kaku
AU  - Nakano K
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan.
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Ohtani, Kisho
AU  - Ohtani K
FAU - Zhao, Gang
AU  - Zhao G
FAU - Funakoshi, Kota
AU  - Funakoshi K
FAU - Ihara, Yoshiko
AU  - Ihara Y
FAU - Sunagawa, Kenji
AU  - Sunagawa K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061128
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
SB  - IM
MH  - Adenoviruses, Human/genetics
MH  - Animals
MH  - Antibody Formation
MH  - Chemokine CCL2/antagonists & inhibitors/*genetics
MH  - Coronary Restenosis/pathology/*therapy
MH  - Disease Models, Animal
MH  - Drug Delivery Systems
MH  - Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Macaca fascicularis
MH  - Male
MH  - Rabbits
MH  - Stents/*adverse effects
MH  - Transfection
MH  - Tunica Intima/pathology
EDAT- 2006/11/28 09:00
MHDA- 2007/12/28 09:00
CRDT- 2006/11/28 09:00
PHST- 2006/06/29 00:00 [received]
PHST- 2006/09/27 00:00 [revised]
PHST- 2006/10/18 00:00 [accepted]
PHST- 2006/11/28 09:00 [pubmed]
PHST- 2007/12/28 09:00 [medline]
PHST- 2006/11/28 09:00 [entrez]
AID - S0021-9150(06)00649-6 [pii]
AID - 10.1016/j.atherosclerosis.2006.10.029 [doi]
PST - ppublish
SO  - Atherosclerosis. 2007 Oct;194(2):309-16. doi: 
      10.1016/j.atherosclerosis.2006.10.029. Epub 2006 Nov 28.