Biomedicines (Oct 2021)

CCR6 Deficiency Increases Infarct Size after Murine Acute Myocardial Infarction

  • David Schumacher,
  • Elisa A. Liehn,
  • Anjana Singh,
  • Adelina Curaj,
  • Erwin Wijnands,
  • Sergio A. Lira,
  • Frank Tacke,
  • Joachim Jankowski,
  • Erik A.L. Biessen,
  • Emiel P.C. van der Vorst

DOI
https://doi.org/10.3390/biomedicines9111532
Journal volume & issue
Vol. 9, no. 11
p. 1532

Abstract

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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.

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