MCP-1 induces cardioprotection against ischaemia/reperfusion injury: Role of reactive oxygen species

Hajime Morimoto, Masamichi Hirose, Masafumi Takahashi, Masanori Kawaguchi, Hirohiko Ise, Pappachan E. Kolattukudy, Mitsuhiko Yamada, Uichi Ikeda

Research output: Contribution to journalArticle

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Abstract

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 α-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 KATP channel-independent pathway; this provides new insight into the beneficial role of MCP-1 in the pathophysiology of ischaemic heart diseases.

Original languageEnglish
Pages (from-to)554-562
Number of pages9
JournalCardiovascular research
Volume78
Issue number3
DOIs
Publication statusPublished - Jun 1 2008

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Reperfusion Injury
Reactive Oxygen Species
Reperfusion
Ischemia
Left Ventricular Dysfunction
Myocardial Ischemia
Cardiac Myosins
KATP Channels
Myosin Heavy Chains
Chemokine CCL2
NADPH Oxidase
Ventricular Pressure
Cardiac Myocytes
Superoxides
Transgenic Mice
Superoxide Dismutase
Apoptosis
Blood Pressure
Messenger RNA
Genes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Morimoto, H., Hirose, M., Takahashi, M., Kawaguchi, M., Ise, H., Kolattukudy, P. E., ... Ikeda, U. (2008). MCP-1 induces cardioprotection against ischaemia/reperfusion injury: Role of reactive oxygen species. Cardiovascular research, 78(3), 554-562. https://doi.org/10.1093/cvr/cvn035

MCP-1 induces cardioprotection against ischaemia/reperfusion injury : Role of reactive oxygen species. / Morimoto, Hajime; Hirose, Masamichi; Takahashi, Masafumi; Kawaguchi, Masanori; Ise, Hirohiko; Kolattukudy, Pappachan E.; Yamada, Mitsuhiko; Ikeda, Uichi.

In: Cardiovascular research, Vol. 78, No. 3, 01.06.2008, p. 554-562.

Research output: Contribution to journalArticle

Morimoto, H, Hirose, M, Takahashi, M, Kawaguchi, M, Ise, H, Kolattukudy, PE, Yamada, M & Ikeda, U 2008, 'MCP-1 induces cardioprotection against ischaemia/reperfusion injury: Role of reactive oxygen species', Cardiovascular research, vol. 78, no. 3, pp. 554-562. https://doi.org/10.1093/cvr/cvn035
Morimoto, Hajime ; Hirose, Masamichi ; Takahashi, Masafumi ; Kawaguchi, Masanori ; Ise, Hirohiko ; Kolattukudy, Pappachan E. ; Yamada, Mitsuhiko ; Ikeda, Uichi. / MCP-1 induces cardioprotection against ischaemia/reperfusion injury : Role of reactive oxygen species. In: Cardiovascular research. 2008 ; Vol. 78, No. 3. pp. 554-562.
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