arly coronary reperfusion limits myocardial damage and improves survival after myocardial infarction. However, growing evidence indicates that reperfusion itself can cause damage to the ischemic myocardium; this damage is known as post-ischemic myocardial reperfusion injury. 1 Local and systemic inflammatory reactions play a key role in the extension of myocardial tissue injury and adverse effects during left ventricular (LV) recovery. 2 Some experimental studies have demonstrated the importance of monocyte/macrophage infiltration after myocardial infarction. 3,4 Monocyte chemoattractant protein-1 (MCP-1) belongs to the CC chemokine subfamily with 2 adjacent cysteine residues, and serves as a chemotactic and activating factor for the recruitment of monocytes. 5 MCP-1 is secreted by various types of cells, such as monocytes/macrophages, T lymphocytes, endothelial cells, vascular smooth muscle cells and myocytes. [5][6][7] Many experimental and clinical studies have demonstrated up-regulation of MCP-1 after myocardial infarction, with recruitment of monocytes/macrophages to the ischemic myocardium. 8,9 CC chemokine receptor 2 (CCR2) is a major receptor for MCP-1 and MCP-1 appears to bind solely to CCR2. 5 We have previously reported improvement in LV remodeling after myocardial infarction in mice deficient in the gene encoding CCR2 by inhibiting matrix metalloproteinase (MMP) activity. 10 Recently, Dewald et al also reported that MCP-1 -/-mice attenuated LV remodeling after myocardial ischemia followed by reperfusion. 11 In addition to the effects on MMP activity and the release of pro-inflammatory cytokines, macrophages may cause oxidative stress. 12-14 Increased oxidative stress has been implicated in the cell death associated with cardiovascular diseases including ischemia-reperfusion injury. 15 Macrophages have been shown to produce peroxynitrite (ONOO -), a highly reactive oxygen species that can cause cell injury. 16 Several studies have implicated peroxynitrite as a major cause of injury in the heart subjected to ischemiareperfusion or cytokines. 17,18 However, it is not clear whether the inhibition of the CCR2 pathway may attenuate oxidative stress induced by myocardial ischemia-reperfusion in mice. We hypothesized that the inhibition of the MCP-1/CCR2 pathway may contribute to the attenuation of infarct size after myocardial ischemia-reperfusion via inhibition of macrophage-related oxidative stress and MMP.Thus, the purpose of the present study was to investigate the relationship between the monocytic inflammatory response and myocardial ischemia-reperfusion injury by using mice deficient in the CCR2 gene. Background Monocyte chemoattractant protein-1 (MCP-1) and its major receptor, CC chemokine receptor 2 (CCR2), have been shown to contribute to left ventricular remodeling after myocardial infarction. However, it is unknown whether CCR2 deficiency protects the myocardium after myocardial ischemia-reperfusion. The purpose of the present study was to investigate the effects of CCR2 deficiency on myocardial...