Blockade of the Monocyte Chemoattractant Protein-1 Receptor Pathway Ameliorates Myocardial Injury in Animal Models of Ischemia and Reperfusion

BACKGROUND: Myocardial infarction is accompanied by inflammatory responses that lead to the recruitment of leukocytes and subsequent myocardial damage and healing. Monocyte chemoattractant protein-1 (MCP-1, also known as CC chemokine ligand 2) and its receptor CC chemokine receptor 2 play a central role in the inflammatory response and myocardial injury after ischemia/reperfusion (I/R). METHODS: Male adult C57BL/6 mice were anesthetized, and the left anterior descending coronary artery was ligated for 30 min. After reperfusion for 3 days, the ischemia and infarct sizes were determined. RESULTS: The treatment of C57BL/6 mice with anti-MCP-1 reduced the infarct size and lessened myocardial inflammation. Furthermore, anti-MCP-1 prevented I/R-induced caspase-3/7 and -8 activities and reduced apoptosis. The treatment of operated mice with anti-MCP-1 shortly before the induction of myocardial ischemia resulted in a reversal of the infarction and improvements in histologic parameters. CONCLUSION: These findings demonstrate a pathogenic role for MCP-1 in animal models of I/R and support the consideration of MCP-1 as a therapeutic target in myocardial ischemia.