CCR6 Deficiency Increases Infarct Size after Murine Acute Myocardial Infarction

Ischemia-reperfusion injury after the reopening of an occluded coronary artery is a major cause of cardiac damage and inflammation after acute myocardial infarction. The chemokine axis CCL20-CCR6 is a key player in various inflammatory processes, including atherosclerosis; however, its role in ischemia-reperfusion injury has remained elusive. Therefore, to gain more insight into the role of the CCR6 in acute myocardial infarction, we have studied cardiac injury after transient ligation of the left anterior descending coronary artery followed by reperfusion in Ccr6(-/-) mice and their respective C57Bl/6 wild-type controls. Surprisingly, Ccr6(-/-) mice demonstrated significantly reduced cardiac function and increased infarct sizes after ischemia/reperfusion. This coincided with a significant increase in cardiac inflammation, characterized by an accumulation of neutrophils and inflammatory macrophage accumulation. Chimeras with a bone marrow deficiency of CCR6 mirrored this adverse Ccr6(-/-) phenotype, while cardiac injury was unchanged in chimeras with stromal CCR6 deficiency. This study demonstrates that CCR6-dependent (bone marrow) cells exert a protective role in myocardial infarction and subsequent ischemia-reperfusion injury, supporting the notion that augmenting CCR6-dependent immune mechanisms represents an interesting therapeutic target.

Automated summary

The study found that CCR6 plays an important role in ischemia-reperfusion injury after acute myocardial infarction, exerting protective effects on the heart through bone marrow cells. Increasing CCR6-dependent immune mechanisms may represent an interesting therapeutic target for cardiac damage and inflammation.