Aims
Over-activation of cellular inflammatory effectors adversely affects myocardial function after acute myocardial infarction (AMI). The CC-chemokine CCL21 is, via its receptor CCR7, one of the key regulators of inflammation and immune cell recruitment, participates in various inflammatory disorders, including cardiovascular ones. This study explored the therapeutic effect of an anti-CCL21 antibody in cardiac remodeling after myocardial infarction.
Background/aims
Over-activation of cellular inflammatory effectors adversely affects myocardial function after acute myocardial infarction (AMI). The CC-chemokine CCL21 is, via its receptor CCR7, one of the key regulators of inflammation and immune cell recruitment, participates in various inflammatory disorders, including cardiovascular ones. This study explored the therapeutic effect of an anti-CCL21 antibody in cardiac remodeling after myocardial infarction.
Conclusions
Our study indicated that CCL21 was involved in cardiac remodeling post infarction and anti-CCL21 strategies might be useful in the treatment of AMI.
Results
An animal model of AMI generated by left anterior descending coronary artery ligation in C57BL/6 mice resulted in higher levels of circulating CCL21 and cardiac CCR7. Neutralization of CCL21 by intravenous injection of anti-CCL21 monoclonal antibody reduced infarct size after AMI, decreased serum levels of neutrophil and monocyte chemo attractants post AMI, diminished neutrophil and macrophage recruitment in infarcted myocardium, and suppressed MMP-9 and total collagen content in myocardium. Anti-CCL21 treatment also limited cardiac enlargement and improved left ventricular function. Conclusions: Our study indicated that CCL21 was involved in cardiac remodeling post infarction and anti-CCL21 strategies might be useful in the treatment of AMI.