PMID- 18267955
OWN - NLM
STAT- MEDLINE
DCOM- 20080909
LR  - 20171116
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 78
IP  - 3
DP  - 2008 Jun 1
TI  - MCP-1 induces cardioprotection against ischaemia/reperfusion injury: role of 
      reactive oxygen species.
PG  - 554-62
LID - 10.1093/cvr/cvn035 [doi]
AB  - AIMS: Monocyte chemoattractant protein-1 (MCP-1: CCL2) has been demonstrated to 
      be involved in the pathophysiology of ischaemic heart disease; however, the 
      precise role of MCP-1 in ischaemia/reperfusion (I/R) injury is controversial. 
      Here, we investigated the role of cardiac MCP-1 expression on left ventricular 
      (LV) dysfunction after global I/R in Langendorff-perfused hearts isolated from 
      transgenic mice expressing the mouse JE-MCP-1 gene under the control of the 
      alpha-cardiac myosin heavy chain promoter (MHC/MCP-1 mice). METHODS AND RESULTS: 
      In vitro experiments showed that MCP-1 prevented the apoptosis of murine neonatal 
      cardiomyocytes after hypoxia/reoxygenation. I/R significantly increased the mRNA 
      expression of MCP-1 in the Langendorff-perfused hearts of wild-type mice. Cardiac 
      MCP-1 overexpression in the MHC/MCP-1 mice improved LV dysfunction after I/R 
      without affecting coronary flow; in particular, it ameliorated LV diastolic 
      pressure after reperfusion. This improvement was independent of both sarcolemmal 
      and mitochondrial K(ATP) channels. Cardiac MCP-1 overexpression prevented 
      superoxide generation in the I/R hearts, and these hearts showed decreased 
      expression of the NADPH oxidase family proteins Nox1, gp91phox, and Nox3 compared 
      with the hearts of wild-type mice. Further, superoxide dismutase activity in the 
      hearts of MHC/MCP-1 mice was significantly increased compared with that in the 
      hearts of wild-type mice. CONCLUSION: These findings suggest that cardiac MCP-1 
      prevented LV dysfunction after global I/R through a reactive oxygen 
      species-dependent but K(ATP) channel-independent pathway; this provides new 
      insight into the beneficial role of MCP-1 in the pathophysiology of ischaemic 
      heart diseases.
FAU - Morimoto, Hajime
AU  - Morimoto H
AD  - Department of Cardiovascular Medicine, Shinshu University Graduate School of 
      Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
FAU - Hirose, Masamichi
AU  - Hirose M
FAU - Takahashi, Masafumi
AU  - Takahashi M
FAU - Kawaguchi, Masanori
AU  - Kawaguchi M
FAU - Ise, Hirohiko
AU  - Ise H
FAU - Kolattukudy, Pappachan E
AU  - Kolattukudy PE
FAU - Yamada, Mitsuhiko
AU  - Yamada M
FAU - Ikeda, Uichi
AU  - Ikeda U
LA  - eng
GR  - HL-69458/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 - 20080210
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Isoenzymes)
RN  - 0 (KATP Channels)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 3.6.1.- (Ventricular Myosins)
RN  - EC 3.6.4.1 (Myosin Heavy Chains)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis
MH  - Cardiotonic Agents/*metabolism
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Isoenzymes/metabolism
MH  - KATP Channels/antagonists & inhibitors/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Myocardial Reperfusion Injury/complications/*metabolism
MH  - Myocytes, Cardiac/drug effects/enzymology/*metabolism/pathology
MH  - Myosin Heavy Chains/genetics
MH  - NADPH Oxidases/metabolism
MH  - *Oxidative Stress/drug effects
MH  - Potassium Channel Blockers/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Superoxide Dismutase/metabolism
MH  - Time Factors
MH  - Ventricular Dysfunction, Left/etiology/metabolism/*prevention & control
MH  - Ventricular Myosins/genetics
MH  - Ventricular Pressure
EDAT- 2008/02/13 09:00
MHDA- 2008/09/10 09:00
CRDT- 2008/02/13 09:00
PHST- 2008/02/13 09:00 [pubmed]
PHST- 2008/09/10 09:00 [medline]
PHST- 2008/02/13 09:00 [entrez]
AID - cvn035 [pii]
AID - 10.1093/cvr/cvn035 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2008 Jun 1;78(3):554-62. doi: 10.1093/cvr/cvn035. Epub 2008 Feb 
      10.