PMID- 14517168
OWN - NLM
STAT- MEDLINE
DCOM- 20031124
LR  - 20220409
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 108
IP  - 17
DP  - 2003 Oct 28
TI  - Anti-monocyte chemoattractant protein-1 gene therapy attenuates left ventricular 
      remodeling and failure after experimental myocardial infarction.
PG  - 2134-40
AB  - BACKGROUND: Increased expression of monocyte chemoattractant protein-1 (MCP-1) 
      has recently been described in clinical and experimental failing heart. However, 
      its pathophysiological significance in heart failure remains obscure. We thus 
      determined whether MCP-1 is increased in post-myocardial infarction (MI) hearts 
      and its blockade can attenuate the development of left ventricular (LV) 
      remodeling and failure. METHODS AND RESULTS: Anterior MI was produced in mice by 
      ligating the left coronary artery. After 4 weeks, MI mice exerted LV dilatation 
      and contractile dysfunction in association with myocyte hypertrophy and 
      interstitial fibrosis of noninfarcted LV. MCP-1 mRNA levels were increased by 
      40-fold in noninfarcted LV 1 day after ligation, which persisted until 28 days. 
      To block the MCP-1 signals, an N-terminal deletion mutant of the human MCP-1 gene 
      was transfected into the limb skeletal muscle 3 days before and 14 days after 
      ligation. This method improved the survival rate of mice with MI at 4 weeks (61% 
      versus 87%, P<0.05) as well as attenuated LV cavity dilatation and contractile 
      dysfunction, interstitial fibrosis, recruitment of macrophages, and myocardial 
      gene expression of tumor necrosis factor-alpha and transforming growth 
      factor-beta compared with the nontreated MI mice despite the comparable infarct 
      size calculated as percent LV circumference. CONCLUSIONS: The activation of MCP-1 
      expression contributes to the LV remodeling and failure after MI. An anti-MCP-1 
      gene therapy can be a useful novel strategy for preventing post-MI heart failure.
FAU - Hayashidani, Shunji
AU  - Hayashidani S
AD  - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
FAU - Tsutsui, Hiroyuki
AU  - Tsutsui H
FAU - Shiomi, Tetsuya
AU  - Shiomi T
FAU - Ikeuchi, Masaki
AU  - Ikeuchi M
FAU - Matsusaka, Hidenori
AU  - Matsusaka H
FAU - Suematsu, Nobuhiro
AU  - Suematsu N
FAU - Wen, Jing
AU  - Wen J
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Takeshita, Akira
AU  - Takeshita A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030929
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Chemokine CCL2/*antagonists & inhibitors/biosynthesis/genetics
MH  - Cytokines/biosynthesis
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Gene Expression Regulation/drug effects
MH  - Genetic Therapy/*methods
MH  - Heart Failure/etiology/pathology/*prevention & control
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Matrix Metalloproteinases/biosynthesis
MH  - Mice
MH  - Muscle, Skeletal/metabolism
MH  - Myocardial Infarction/*complications/pathology
MH  - Myocardium/metabolism/pathology
MH  - Sequence Deletion/genetics
MH  - Survival Rate
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Ventricular Dysfunction, Left/etiology/therapy
MH  - Ventricular Remodeling/*genetics
EDAT- 2003/10/01 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/10/01 05:00
PHST- 2003/10/01 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/10/01 05:00 [entrez]
AID - 01.CIR.0000092890.29552.22 [pii]
AID - 10.1161/01.CIR.0000092890.29552.22 [doi]
PST - ppublish
SO  - Circulation. 2003 Oct 28;108(17):2134-40. doi: 
      10.1161/01.CIR.0000092890.29552.22. Epub 2003 Sep 29.