PMID- 17543688
OWN - NLM
STAT- MEDLINE
DCOM- 20070713
LR  - 20121115
IS  - 0741-5214 (Print)
IS  - 0741-5214 (Linking)
VI  - 45
IP  - 6
DP  - 2007 Jun
TI  - Blockade of monocyte chemoattractant protein-1 by adenoviral gene transfer 
      inhibits experimental vein graft neointimal formation.
PG  - 1236-43
AB  - BACKGROUND: Clinical outcome of vascular bypass surgery using autologous vein 
      graft is limited by neointimal formation associated with vein graft failure. 
      Because inflammatory changes are one of the main pathologic features of vein 
      graft failure, monocyte chemoattractant protein-1 (MCP-1) might therefore 
      underlie in the mechanism of vein graft failure. There is no direct evidence, 
      however, that shows the benefits of local anti-MCP-1 therapy as a novel molecular 
      approach for prevention of vein graft failure. METHODS: To block MCP-1, we used 
      an N-terminal deletion mutant of the MCP-1 gene (7ND), which lacks the N-terminal 
      amino acids 2 to 8, binds to its receptor CCR2, and blocks MCP-1-mediated 
      monocyte chemotaxis. 7ND works as dominant-negative inhibitor of MCP-1. 
      Autologous canine jugular vein grafts were transfected by incubating them ex vivo 
      in a solution with or without adenovirus vectors containing 7ND gene or LacZ 
      gene, and interposed into the carotid arteries. RESULTS: Adenovirus-mediated gene 
      transfer of 7ND, but not LacZ gene transfer, significantly attenuated 
      inflammation (monocyte infiltration per mm2 on day 7: 328+/-59, 220+/-11, 26+/-4 
      in control, LacZ, and 7ND groups, respectively, P<.05, n=4 each) and 
      proliferation (appearance of proliferating cells per mm2 on day 7: 1005+/-186, 
      756+/-106, 252+/-27 in control, LacZ, and 7ND groups, P<.05, n=4 each) at 7 days 
      after the operation and thus suppressed neointimal formation (neointimal area in 
      mm2 on day 28: 1.63+/-0.51, 1.96+/-0.48, 0.68+/-0.10 in control, LacZ, and 7ND 
      groups, P<.05, n=4 each). This strategy also attenuated upregulation of MCP-1 
      activities but did not affect endothelial regeneration process. CONCLUSIONS: 
      Blockade of MCP-1 by adenoviral gene transfer of 7ND limits neointimal formation 
      associated with vein graft failure in dogs. This study highlights the potential 
      therapeutic benefit of local anti-MCP-1 therapy for prevention of neointimal 
      formation associated with vein graft failure.
FAU - Tatewaki, Hideki
AU  - Tatewaki H
AD  - Department of Surgery, Graduate School of Medical Science, Kyushu University, 
      Fukuoka, Japan.
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Kimura, Satoshi
AU  - Kimura S
FAU - Nishida, Takahiro
AU  - Nishida T
FAU - Morita, Shigeki
AU  - Morita S
FAU - Tominaga, Ryuji
AU  - Tominaga R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Vasc Surg
JT  - Journal of vascular surgery
JID - 8407742
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Anastomosis, Surgical
MH  - Animals
MH  - Carotid Arteries/*surgery
MH  - Cell Proliferation
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Dogs
MH  - Endothelium, Vascular/metabolism/pathology
MH  - Genetic Therapy/*methods
MH  - *Genetic Vectors
MH  - Graft Rejection/genetics/metabolism/pathology/*prevention & control
MH  - Hyperplasia
MH  - Inflammation/metabolism/prevention & control
MH  - Jugular Veins/metabolism/pathology/*transplantation
MH  - Male
MH  - Mutation
MH  - Time Factors
MH  - Transfection
MH  - Transplantation, Autologous
MH  - Tunica Intima/metabolism/*pathology
EDAT- 2007/06/05 09:00
MHDA- 2007/07/14 09:00
CRDT- 2007/06/05 09:00
PHST- 2006/10/10 00:00 [received]
PHST- 2007/01/29 00:00 [accepted]
PHST- 2007/06/05 09:00 [pubmed]
PHST- 2007/07/14 09:00 [medline]
PHST- 2007/06/05 09:00 [entrez]
AID - S0741-5214(07)00232-7 [pii]
AID - 10.1016/j.jvs.2007.01.066 [doi]
PST - ppublish
SO  - J Vasc Surg. 2007 Jun;45(6):1236-43. doi: 10.1016/j.jvs.2007.01.066.