TY - JOUR
T1 - Cardiac monocytes and macrophages after myocardial infarction
AU - Peet, Claire
AU - Ivetic, Aleksandar
AU - Bromage, Daniel Ian
AU - Shah, Ajay Manmohan
PY - 2019/12/16
Y1 - 2019/12/16
N2 - 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 summarise 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.
AB - 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 summarise 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.
UR - https://www.scopus.com/pages/publications/85082066801
U2 - 10.1093/cvr/cvz336
DO - 10.1093/cvr/cvz336
M3 - Article
SN - 0008-6363
JO - Cardiovascular Research
JF - Cardiovascular Research
M1 - cvz336
ER -
