Preserving Endogenous Cardiac Macrophages Following Heart Attack Reduces Scarring and Promotes Healing

Louis, MO, USA) found, however, that following injury to the adult heart, this pool of endogenous macrophages is overrun and crowded out by pro-inflammatory macrophages derived from monocytes that migrate to the site of injury from the bone marrow.

The two types of macrophages can be distinguished by expression of the surface marker CCR2 (C-C chemokine receptor type 2). Macrophages without CCR2 originate in the heart; those with CCR2 come from the bone marrow. CCR2 is a receptor for monocyte chemoattractant protein-1 (CCL2), which is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors.

The investigators induced injuries in a neonatal mouse model that mimicked the damage caused by a heart attack to the adult human heart. They reported in the October 27, 2014, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that preventing recruitment of monocyte-derived macrophages to the adult heart preserved endogenous cardiac macrophage subsets, reduced inflammation, and enhanced tissue repair. These findings indicated that endogenous macrophages were key mediators of cardiac recovery and suggested that therapeutics targeting distinct macrophage lineages might serve as novel treatments for heart failure.

“Researchers have known for a long time that the neonatal mouse heart can recover well from injury, and in some cases can even regenerate,” said first author Dr. Kory J. Lavine, instructor in medicine at the Washington University School of Medicine. “If you cut off the lower tip of the neonatal mouse heart, it can grow back. But if you do the same thing to an adult mouse heart, it forms scar tissue. The same macrophages that promote healing after injury in the neonatal heart also are present in the adult heart, but they seem to go away with injury. This may explain why the young heart can recover while the adult heart cannot.”

“When we chemically blocked CCR2 expression, we found that the macrophages from the bone marrow did not come in,” said Dr. Lavine. “And the macrophages native to the heart remained. We saw reduced inflammation in these injured adult hearts, less oxidative damage and improved repair. We also saw new blood vessel growth. By blocking the CCR2 signaling, we were able to keep the resident macrophages around and promote repair.”

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Washington University School of Medicine