Mending a Broken Heart

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Researchers identify an immune cell that promotes the repair of heart tissue.
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The findings reveal that neonatal macrophages, which are effective at triggering the growth of heart muscle cells in newborn babies, are still present in the adult heart before a heart attack.

Scientists at the Peter Munk Cardiac Centre have identified a cell that is key to helping the heart repair and potentially regenerate following a heart attack.

The study, published in Nature Immunology, characterized a type of white blood cell—referred to as a cardiac macrophage—that resides in our hearts. Macrophages are well-known for their ability to fight infections and promote tissue repair.

"Using a combination of single-cell technologies, we found that instead of a single type of macrophage, there are at least four types that live within the un-injured heart,” says senior author Dr. Slava Epelman, staff cardiologist and scientist at Toronto General Hospital Research Institute. “That number increases to 11 after a heart attack, which indicates the immune system behaves in a much more complex fashion than we ever imagined."

One type of macrophage was found to be in a neonatal-like (or newborn) state, a time in life where these cells would normally aid in the growth and development of organs, meaning that they could be channeled to help repair the heart following a heart attack. These macrophages are lost after a heart attack in adults, which could be a contributing factor as to why the adult heart may not heal itself as well as the neonatal heart.

"Genetically removing neonatal-like macrophages at the time of the heart attack in experimental models worsens heart function most profoundly at the region of the heart separating injured and un-injured heart muscle—the only zone of the adult heart where this macrophage type increases in number," says Dr. Epelman, explaining the important role that these newly identified cardiac macrophages play in repair.

These findings represent an instrumental step forward in finding effective strategies to promote repair following a heart attack.

This work was supported by the Canadian Institutes of Health Research, the Heart and Stroke Foundation, March of Dimes, The Ted Rogers Centre for Heart Research, the Peter Munk Cardiac Centre, the National Institutes of Health and the Toronto General & Western Hospital Foundation. M Cybulsky holds a Tier 1 Canada Research Chair in Arterial Wall Biology and Atherogenesis.

Dick SA, Macklin JA, Nejat S, Momen A, Clemente-Casares X, Althagafi MG, Chen J, Kantores C, Hosseinzadeh S, Aronoff L, Wong A, Zaman R, Barbu I, Besla R, Lavine KJ, Razani B, Ginhoux F, Husain M, Cybulsky MI, Robbins CS, Epelman S. Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction. Nat Immunol. 2019 Jan;20(1):29-39. doi: 10.1038/s41590-018-0272-2.

 

Dr. Slava Epelman, senior author of the study, is pictured above conducting experiments in his laboratory (L) and in a flow cytometry facility (R).