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Role of Macrophages in Cardioprotection

Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813, USA
Tecnologico de Monterrey, Centro de Biotecnologia-FEMSA, Monterrey, NL 264610, Mexico
National Heart Research Institute Singapore, National Heart Centre, Singapore 169609, Singapore
Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore 169857, Singapore
Institute of Biochemistry, Medical School, Justus-Liebig University, 35392 Giessen, Germany
Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia
Yong Loo Lin School of Medicine, National University Singapore, Singapore 117597, Singapore
The Hatter Cardiovascular Institute, University College London, London WC1E 6HX, UK
The National Institute of Health Research University College London Hospitals Biomedical Research Centre, Research & Development, London W1T 7DN, UK
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(10), 2474;
Received: 31 March 2019 / Revised: 14 May 2019 / Accepted: 17 May 2019 / Published: 19 May 2019
PDF [645 KB, uploaded 19 May 2019]


Cardiovascular diseases are the leading cause of mortality worldwide. It is widely known that non-resolving inflammation results in atherosclerotic conditions, which are responsible for a host of downstream pathologies including thrombosis, myocardial infarction (MI), and neurovascular events. Macrophages, as part of the innate immune response, are among the most important cell types in every stage of atherosclerosis. In this review we discuss the principles governing macrophage function in the healthy and infarcted heart. More specifically, how cardiac macrophages participate in myocardial infarction as well as cardiac repair and remodeling. The intricate balance between phenotypically heterogeneous populations of macrophages in the heart have profound and highly orchestrated effects during different phases of myocardial infarction. In the early “inflammatory” stage of MI, resident cardiac macrophages are replaced by classically activated macrophages derived from the bone marrow and spleen. And while the macrophage population shifts towards an alternatively activated phenotype, the inflammatory response subsides giving way to the “reparative/proliferative” phase. Lastly, we describe the therapeutic potential of cardiac macrophages in the context of cell-mediated cardio-protection. Promising results demonstrate innovative concepts; one employing a subset of yolk sac-derived, cardiac macrophages that have complete restorative capacity in the injured myocardium of neonatal mice, and in another example, post-conditioning of cardiac macrophages with cardiosphere-derived cells significantly improved patient’s post-MI diagnoses. View Full-Text
Keywords: macrophages; cardioprotection; innate immune response; myocardial infarction; cardiac repair; remodeling macrophages; cardioprotection; innate immune response; myocardial infarction; cardiac repair; remodeling

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Yap, J.; Cabrera-Fuentes, H.A.; Irei, J.; Hausenloy, D.J.; Boisvert, W.A. Role of Macrophages in Cardioprotection. Int. J. Mol. Sci. 2019, 20, 2474.

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