Improvements in early interventions after acute myocardial infarction (AMI), notably, the increased use of timely reperfusion therapy, have increased survival dramatically in recent decades. Despite this, maladaptive ventricular remodelling and subsequent heart failure (HF) following AMI remain a significant clinical challenge, particularly because several pre-clinical strategies to attenuate remodelling have failed to translate into clinical practice. Monocytes and macrophages, pleiotropic cells of the innate immune system, are integral in both the initial inflammatory response to injury and subsequent wound healing in many tissues, including the heart. However, maladaptive immune cell behaviour contributes to ventricular remodelling in mouse models, prompting experimental efforts to modulate the immune response to prevent the development of HF. Seminal work in macrophage biology defined macrophages as monocyte-derived cells that are comprised of two populations, pro-inflammatory M1 macrophages and reparative M2 macrophages, and initial investigations into cardiac macrophage populations following AMI suggested they aligned well to this model. However, more recent data, in the heart and other tissues, demonstrate remarkable heterogeneity and plasticity in macrophage development, phenotype, and function. These recent insights into macrophage biology may explain the failure of non-specific immunosuppressive strategies and offer novel opportunities for therapeutic targeting to prevent HF following AMI. Here, we summarize the traditional monocyte-macrophage paradigm, experimental evidence for the significance of these cells in HF after AMI, and the potential relevance of emerging evidence that refutes canonical models of monocyte and macrophage biology.
Keywords: Macrophage; Monocyte; Myocardial infarction.
© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.