Myocardial infarction (MI), as a result of thrombosis or vascular occlusion, is the most prevalent cause of morbidity and mortality among all cardiovascular diseases. The devastating consequences of MI are compounded by the complexities of cellular functions involved in the initiation and resolution of early-onset inflammation and the longer-term effects related to scar formation. The resultant tissue damage can occur as early as 1 h after MI and activates inflammatory signalling pathways to elicit an immune response. Macrophages are one of the most active cell types during all stages after MI, including the cardioprotective, inflammatory and tissue repair phases. In this Review, we describe the phenotypes of cardiac macrophage involved in MI and their cardioprotective functions. A specific subset of macrophages called resident cardiac macrophages (RCMs) are derived from yolk sac progenitor cells and are maintained as a self-renewing population, although their numbers decrease with age. We explore sophisticated sequencing techniques that demonstrate the cardioprotective properties of this cardiac macrophage phenotype. Furthermore, we discuss the interactions between cardiac macrophages and other important cell types involved in the pathology and resolution of inflammation after MI. We summarize new and promising therapeutic approaches that target macrophage-mediated inflammation and the cardioprotective properties of RCMs after MI. Finally, we discuss future directions for the study of RCMs in MI and cardiovascular health in general.
Macrophages are one of the most active cell types participating in the cardiac remodelling events that occur during the inflammatory, proliferative and reparative phases after a myocardial infarction (MI).
Immediately after an MI, macrophages that accumulate in the infarcted heart tissue are derived from either the bone marrow or splenic reservoirs and produce cytokines that mediate inflammation.
Resident cardiac macrophages have an essential role in the development and functioning of the normal heart, whereas after an MI, the surviving resident cardiac macrophages act to offset the inflammatory response mediated by recruited macrophages.
In the infarcted heart, macrophages interact with several cell types, including cardiomyocytes, endothelial cells, fibroblasts and lymphocytes, that contribute to the cardiac remodelling that occurs after an MI.
A deeper understanding of the role of macrophages in the infarcted heart might lead to macrophage-specific therapeutic approaches to mitigate tissue damage after an MI.
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The authors are grateful to L. N. Boisvert (John A. Burns School of Medicine, University of Hawaii, USA) for her expert editing of the manuscript before submission.
The authors declare no competing interests.
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Yap, J., Irei, J., Lozano-Gerona, J. et al. Macrophages in cardiac remodelling after myocardial infarction. Nat Rev Cardiol (2023). https://doi.org/10.1038/s41569-022-00823-5