Study Reveals Why Newborns Can Regenerate Heart Tissue While Adults Struggle After a Heart Attack
A new study in experimental animals reveals a critical difference in how macrophages-a part of the immune system-help repair the heart in newborns versus adults after a heart attack. The study highlights a fundamental difference in how the immune system drives healing based on age. The study was published in the journal Immunity.
In newborns, macrophages perform a process called efferocytosis, which recognizes and eats dying cells. This process triggers the production of a bioactive lipid called thromboxane, signaling nearby heart muscle cells to divide, and allowing the heart to regenerate damaged heart muscle, the study found. In adults, macrophages produce much less thromboxane, leading to a weaker repair signal.
The study examined how the immune system responds to heart injury in mice of different ages, including newborn mice (one-day old) and adult mice (eight weeks old). The researchers found the ability of macrophages to engulf dying cells was enhanced in newborn mice due to increased expression of MerTK, a receptor that recognizes dying cells. Therefore, when the scientists blocked this key receptor, newborn mice lost their ability to regenerate their hearts, resembling adult hearts after a heart attack.
Engulfment of dying cells by newborn macrophages triggered a chemical chain reaction that produced a molecule called thromboxane A2, which unexpectedly stimulated heart muscle cells to multiply and repair the damage, the study found. Additionally, nearby muscle heart cells in newborns are primed to respond to thromboxane A2, leading them to change their metabolism to support their growth and healing. But in adults, this process did not work the same way — after an injury, their macrophages did not produce enough thromboxane A2, limiting their ability to regenerate heart tissue.
Reference: Connor Lantz, Amanda Becker, Matthew DeBerge, Mallory Filipp, Kristofor Glinton, Aparnaa Ananthakrishnan, Jessica Urbanczyk, Madeline Cetlin, Afnan Alzamroon, Ahmed Abdel-Latif, Matthew Spite, Zhi-Dong Ge, Edward B. Thorp, Early-age efferocytosis directs macrophage arachidonic acid metabolism for tissue regeneration, Immunity, Volume 58, Issue 2, 2025, Pages 344-361.e7, ISSN 1074-7613, https://doi.org/10.1016/j.immuni.2024.11.018.
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