PMID- 11319201
OWN - NLM
STAT- MEDLINE
DCOM- 20020930
LR  - 20220227
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 103
IP  - 16
DP  - 2001 Apr 24
TI  - New anti-monocyte chemoattractant protein-1 gene therapy attenuates 
      atherosclerosis in apolipoprotein E-knockout mice.
PG  - 2096-101
AB  - BACKGROUND: Monocyte recruitment into the arterial wall and its activation may be 
      the central event in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is 
      an important chemokine for monocyte recruitment, and its receptor (CCR2) may 
      mediate such in vivo response. Although the importance of the MCP-1/CCR2 pathway 
      in atherogenesis has been clarified, it remains unanswered whether postnatal 
      blockade of the MCP-1 signals could be a unique site-specific gene therapy. 
      METHODS AND RESULTS: We devised a new strategy for anti-MCP-1 gene therapy to 
      treat atherosclerosis by transfecting an N-terminal deletion mutant of the human 
      MCP-1 gene into a remote organ (skeletal muscle) in apolipoprotein E-knockout 
      mice. This strategy effectively blocked MCP-1 activity and inhibited the 
      formation of atherosclerotic lesions but had no effect on serum lipid 
      concentrations. Furthermore, this strategy increased the lesional extracellular 
      matrix content. CONCLUSIONS: We conclude that this anti-MCP-1 gene therapy may 
      serve not only to reduce atherogenesis but also to stabilize vulnerable 
      atheromatous plaques. This strategy may be a useful and feasible form of gene 
      therapy against atherosclerosis in humans.
FAU - Ni, W
AU  - Ni W
AD  - Department of Cardiovascular Medicine, Kyushu University, Fukuoka, Japan.
FAU - Egashira, K
AU  - Egashira K
FAU - Kitamoto, S
AU  - Kitamoto S
FAU - Kataoka, C
AU  - Kataoka C
FAU - Koyanagi, M
AU  - Koyanagi M
FAU - Inoue, S
AU  - Inoue S
FAU - Imaizumi, K
AU  - Imaizumi K
FAU - Akiyama, C
AU  - Akiyama C
FAU - Nishida, K I
AU  - Nishida KI
FAU - Takeshita, A
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 (Chemokine CCL2)
RN  - 0 (Lipids)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Animals
MH  - Aorta/drug effects/pathology
MH  - Apolipoproteins E/*deficiency/genetics
MH  - Arteriosclerosis/genetics/*therapy
MH  - Chemokine CCL2/*antagonists & inhibitors/genetics/pharmacology
MH  - Chemotaxis/drug effects
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Genetic Therapy/*methods
MH  - Humans
MH  - Leukocyte Count
MH  - Lipids/blood
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Monocytes/cytology/drug effects
MH  - Muscle, Skeletal/drug effects/metabolism
MH  - Peptide Fragments/genetics/*pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - Sequence Deletion
MH  - Skin/cytology/drug effects
MH  - Transfection
MH  - Treatment Outcome
EDAT- 2001/04/25 10:00
MHDA- 2002/10/02 04:00
CRDT- 2001/04/25 10:00
PHST- 2001/04/25 10:00 [pubmed]
PHST- 2002/10/02 04:00 [medline]
PHST- 2001/04/25 10:00 [entrez]
AID - 10.1161/01.cir.103.16.2096 [doi]
PST - ppublish
SO  - Circulation. 2001 Apr 24;103(16):2096-101. doi: 10.1161/01.cir.103.16.2096.