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
Affiliations
David Schumacher
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany
Elisa A. Liehn
Department of Intensive Care and Intermediate Care, University Hospital, RWTH Aachen University, 52074 Aachen, Germany
Anjana Singh
Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, 6229 ER Maastricht, The Netherlands
Adelina Curaj
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany
Erwin Wijnands
Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, 6229 ER Maastricht, The Netherlands
Sergio A. Lira
Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Frank Tacke
Department of Hepatology and Gastroenterolgy, Campus Virchow-Klinikum and Campus Charité Mitte, Charité–Universitätsmedizin Berlin, 13353 Berlin, Germany
Joachim Jankowski
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany
Erik A.L. Biessen
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany
Emiel P.C. van der Vorst
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany
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.
