Enhanced monocyte recruitment and delayed alternative macrophage polarisation accompanies impaired repair following myocardial infarction in C57BL/6 compared to BALB/c mice

Activation of the innate immune response following myocardial infarction (MI) is essential for infarct repair. Pre-clinical models of MI commonly use C57BL/6 mice, which have a type 1-dominant immune response, whereas other mouse strains such as BALB/c mice have a type 2-dominant immune response. We compared C57BL/6 and BALB/c mice to investigate whether predisposition towards a pro-inflammatory phenotype influences the dynamics of the innate immune response to MI and associated infarct healing and the risk of cardiac rupture. MI was induced by permanent coronary artery ligation in 12-15 week-old male wild-type BALB/c and C57BL/6 mice. Prior to MI, C57BL/6 mice had a lower proportion of CD206+ anti-inflammatory macrophages in the heart and an expanded blood pool of pro-inflammatory Ly6Chi monocytes in comparison to BALB/c mice. The systemic inflammatory response in C57BL/6 mice following MI was more pronounced with greater peripheral blood Ly6Chi monocytosis, splenic Ly6Chi monocyte mobilisation and myeloid cell infiltration of pericardial adipose tissue. This led to an increased and prolonged macrophage accumulation, as well as delayed transition towards anti-inflammatory macrophage polarisation in the infarct zone and surrounding tissues of C57BL/6 mice. These findings accompanied a higher rate of mortality due to cardiac rupture in C57BL/6 mice compared with BALB/c mice. We conclude that lower post-MI survival of C57BL/6 mice over BALB/c mice is mediated in part by a more pronounced and prolonged inflammatory response. Outcomes in BALB/c mice highlight the therapeutic potential of modulating resolution of the innate immune response following MI for the benefit of successful infarct healing. This article is protected by copyright. All rights reserved.