PMID- 12438296
OWN - NLM
STAT- MEDLINE
DCOM- 20021125
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 106
IP  - 21
DP  - 2002 Nov 19
TI  - Anti-monocyte chemoattractant protein-1 gene therapy limits progression and 
      destabilization of established atherosclerosis in apolipoprotein E-knockout mice.
PG  - 2700-6
AB  - BACKGROUND: Monocyte infiltration into the arterial wall and its activation is 
      the central event in atherogenesis. Thus, monocyte chemoattractant protein-1 
      (MCP-1) might be a novel therapeutic target against atherogenesis. We and others 
      recently reported that blockade or abrogation of the MCP-1 pathway attenuates the 
      initiation of atheroma formation in hypercholesterolemic mice. It remains 
      unclear, however, whether blockade of MCP-1 can limit progression or 
      destabilization of established lesions. METHODS AND RESULTS: We report here that 
      blockade of MCP-1 by transfecting an N-terminal deletion mutant of the MCP-1 gene 
      limited progression of preexisting atherosclerotic lesions in the aortic root in 
      hypercholesterolemic mice. In addition, blockade of MCP-1 changed the lesion 
      composition into a more stable phenotype, ie, containing fewer macrophages and 
      lymphocytes, less lipid, and more smooth muscle cells and collagen. This strategy 
      decreased expression of CD40 and the CD40 ligand in the atherosclerotic plaque 
      and normalized the increased chemokine (RANTES and MCP-1) and cytokine (tumor 
      necrosis factor alpha, interleukin-6, interleukin-1beta, and transforming growth 
      factor beta(1)) gene expression. These data suggest that MCP-1 is a central 
      mediator in the progression and destabilization of established atheroma. 
      CONCLUSIONS: The results of the present study suggest that the inflammatory 
      responses mediated by MCP-1 are important in atherosclerosis and its 
      complications.
FAU - Inoue, Shujiro
AU  - Inoue S
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University, Fukuoka, Japan.
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Ni, Weihua
AU  - Ni W
FAU - Kitamoto, Shiro
AU  - Kitamoto S
FAU - Usui, Makoto
AU  - Usui M
FAU - Otani, Kisho
AU  - Otani K
FAU - Ishibashi, Minako
AU  - Ishibashi M
FAU - Hiasa, Ken-ichi
AU  - Hiasa K
FAU - Nishida, Ken-ichi
AU  - Nishida K
FAU - Takeshita, Akira
AU  - Takeshita A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Apolipoproteins E)
RN  - 0 (CD40 Antigens)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 147205-72-9 (CD40 Ligand)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.- (Mmp13 protein, mouse)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/*deficiency/genetics
MH  - Arteriosclerosis/genetics/pathology/*therapy
MH  - CD40 Antigens/metabolism
MH  - CD40 Ligand/metabolism
MH  - Chemokine CCL2/*antagonists & inhibitors/genetics/metabolism
MH  - Chemokines/genetics/metabolism
MH  - Collagenases/metabolism
MH  - Cytokines/genetics/metabolism
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Hypercholesterolemia/genetics
MH  - Matrix Metalloproteinase 13
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Muscle, Skeletal/drug effects/metabolism
MH  - Peptide Fragments/administration & dosage/genetics
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/metabolism
MH  - Signal Transduction/drug effects/genetics
MH  - T-Lymphocytes/pathology
MH  - Treatment Outcome
MH  - Up-Regulation/drug effects
EDAT- 2002/11/20 04:00
MHDA- 2002/11/26 04:00
CRDT- 2002/11/20 04:00
PHST- 2002/11/20 04:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/11/20 04:00 [entrez]
AID - 10.1161/01.cir.0000038140.80105.ad [doi]
PST - ppublish
SO  - Circulation. 2002 Nov 19;106(21):2700-6. doi: 10.1161/01.cir.0000038140.80105.ad.