Title

Mcp-1 Induces Cardioprotection Against Ischaemia/Reperfusion Injury: Role Of Reactive Oxygen Species

Keywords

Apoptosis; Cytokines; Infection/inflammation; Myocytes; Oxygen radicals

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. © The Author 2008.

Publication Date

6-1-2008

Publication Title

Cardiovascular Research

Volume

78

Issue

3

Number of Pages

554-562

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1093/cvr/cvn035

Socpus ID

44449170800 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/44449170800

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