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

研究成果: ジャーナルへの寄稿学術誌査読

57 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)554-562
ページ数9
ジャーナルCardiovascular research
78
3
DOI
出版ステータス出版済み - 6月 2008
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 生理学
  • 循環器および心血管医学
  • 生理学(医学)

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