CCR6 Deficiency Increases Infarct Size after Murine Acute Myocardial Infarction

Area of Science:

• Cardiovascular Science
• Immunology
• Inflammation Biology

Background:

• Ischemia-reperfusion injury (IRI) following acute myocardial infarction (AMI) causes significant cardiac damage.
• The chemokine axis CCL20-CCR6 is implicated in inflammatory diseases like atherosclerosis, but its role in cardiac IRI is unclear.

Purpose of the Study:

• To investigate the role of C-C chemokine receptor type 6 (CCR6) in cardiac injury and inflammation after myocardial infarction-induced IRI.
• To determine whether CCR6 deficiency impacts cardiac function and infarct size post-ischemia/reperfusion.

Main Methods:

• Utilized a mouse model of transient coronary artery ligation followed by reperfusion.
• Compared cardiac injury, function, and inflammatory cell infiltration in CCR6-deficient mice and wild-type controls.
• Generated bone marrow and stromal chimeras to delineate cell-specific roles of CCR6.

Main Results:

• CCR6-deficient mice exhibited significantly worsened cardiac function and larger infarct sizes after IRI compared to controls.
• Increased neutrophil and inflammatory macrophage accumulation was observed in the hearts of CCR6-deficient mice.
• Bone marrow-derived CCR6 deficiency recapitulated the adverse phenotype, while stromal CCR6 deficiency had no effect.

Conclusions:

• CCR6-expressing bone marrow-derived cells play a crucial protective role in mitigating cardiac damage during myocardial infarction and subsequent IRI.
• Targeting CCR6-dependent immune mechanisms may offer a novel therapeutic strategy for managing cardiac IRI.