Title
MCP-1 induces cardioprotection against ischaemia/reperfusion injury: role of reactive oxygen species
Abbreviated Journal Title
Cardiovasc. Res.
Keywords
apoptosis; cytokines; infection/inflammation; myocytes; oxygen radicals; MONOCYTE CHEMOATTRACTANT PROTEIN-1; EXPERIMENTAL MYOCARDIAL-INFARCTION; SMOOTH-MUSCLE CELLS; MIGRATION IN-VITRO; K-ATP CHANNELS; NADPH OXIDASE; CARDIAC OVEREXPRESSION; INFLAMMATORY RESPONSE; RADICAL GENERATION; REPERFUSION INJURY; Cardiac & Cardiovascular Systems
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 rote of MCP-1 in ischaemia/reperfusion (I/R) injury is controversial. Here, we investigated the role of cardiac MCP-1 expression on left ventricular (I]V) 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.
Journal Title
Cardiovascular Research
Volume
78
Issue/Number
3
Publication Date
1-1-2008
Document Type
Article
DOI Link
Language
English
First Page
554
Last Page
562
WOS Identifier
ISSN
0008-6363
Recommended Citation
"MCP-1 induces cardioprotection against ischaemia/reperfusion injury: role of reactive oxygen species" (2008). Faculty Bibliography 2000s. 745.
https://stars.library.ucf.edu/facultybib2000/745
Comments
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