PMID- 16990567
OWN - NLM
STAT- MEDLINE
DCOM- 20061027
LR  - 20071114
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 99
IP  - 8
DP  - 2006 Oct 13
TI  - Cardiac overexpression of monocyte chemoattractant protein-1 in transgenic mice 
      prevents cardiac dysfunction and remodeling after myocardial infarction.
PG  - 891-9
AB  - Myocardial infarction (MI) is accompanied by inflammatory responses that lead to 
      the recruitment of leukocytes and subsequent myocardial damage, healing, and scar 
      formation. Because monocyte chemoattractant protein-1 (MCP-1) (also known as 
      CCL2) regulates monocytic inflammatory responses, we investigated the effect of 
      cardiac MCP-1 overexpression on left ventricular (LV) dysfunction and remodeling 
      in a murine MI model. Transgenic mice expressing the mouse JE-MCP-1 gene under 
      the control of the alpha-cardiac myosin heavy chain promoter (MHC/MCP-1 mice) 
      were used for this purpose. MHC/MCP-1 mice had reduced infarct area and scar 
      formation and improved LV dysfunction after MI. These mice also showed induction 
      of macrophage infiltration and neovascularization; however, few bone 
      marrow-derived endothelial cells were detected in MHC/MCP-1 mice whose bone 
      marrow was replaced with that of Tie2/LacZ transgenic mice. Flow cytometry 
      analysis showed no increase in endothelial progenitor cells (CD34+/Flk-1+ cells) 
      in MHC/MCP-1 mice. Marked myocardial interleukin (IL)-6 secretion, STAT3 
      activation, and LV hypertrophy were observed after MI in MHC/MCP-1 mice. 
      Furthermore, cardiac myofibroblasts accumulated after MI in MHC/MCP-1 mice. In 
      vitro experiments revealed that a combination of IL-6 with MCP-1 synergistically 
      stimulated and sustained STAT3 activation in cardiomyocytes. MCP-1, IL-6, and 
      hypoxia directly promoted the differentiation of cardiac fibroblasts into 
      myofibroblasts. Our results suggest that cardiac overexpression of MCP-1 induced 
      macrophage infiltration, neovascularization, myocardial IL-6 secretion, and 
      accumulation of cardiac myofibroblasts, thereby resulting in the prevention of LV 
      dysfunction and remodeling after MI. They also provide a new insight into the 
      role of cardiac MCP-1 in the pathophysiology of MI.
FAU - Morimoto, Hajime
AU  - Morimoto H
AD  - Department of Cardiovascular Medicine and Regeneration, Shinshu University 
      Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
FAU - Takahashi, Masafumi
AU  - Takahashi M
FAU - Izawa, Atsushi
AU  - Izawa A
FAU - Ise, Hirohiko
AU  - Ise H
FAU - Hongo, Minoru
AU  - Hongo M
FAU - Kolattukudy, Pappachan E
AU  - Kolattukudy PE
FAU - Ikeda, Uichi
AU  - Ikeda U
LA  - eng
GR  - HL69458/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060921
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Capillaries/physiopathology
MH  - Cardiomegaly/etiology
MH  - Cell Differentiation
MH  - Chemokine CCL2/metabolism/*physiology
MH  - Cicatrix/pathology
MH  - Coronary Vessels/physiopathology
MH  - Cytokines/physiology
MH  - Echocardiography
MH  - Endothelial Cells/cytology/physiology
MH  - Inflammation Mediators/physiology
MH  - Macrophages/pathology
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Transgenic
MH  - Myocardial Infarction/complications/metabolism/pathology/*physiopathology
MH  - Myocardium/*metabolism/pathology
MH  - Neovascularization, Physiologic
MH  - STAT3 Transcription Factor/metabolism
MH  - Ventricular Dysfunction, Left/*prevention & control
MH  - Ventricular Function, Left
MH  - *Ventricular Remodeling
EDAT- 2006/09/23 09:00
MHDA- 2006/10/28 09:00
CRDT- 2006/09/23 09:00
PHST- 2006/09/23 09:00 [pubmed]
PHST- 2006/10/28 09:00 [medline]
PHST- 2006/09/23 09:00 [entrez]
AID - 01.RES.0000246113.82111.2d [pii]
AID - 10.1161/01.RES.0000246113.82111.2d [doi]
PST - ppublish
SO  - Circ Res. 2006 Oct 13;99(8):891-9. doi: 10.1161/01.RES.0000246113.82111.2d. Epub 
      2006 Sep 21.