Newborns with heart complications can rely on their newly developed immune system to regenerate heart tissue, but adults are not that lucky. After a heart attack, it is difficult for most adults to regenerate healthy heart tissue, resulting in the accumulation of scar tissue and heart failure.
A new Northwestern medical study reveals in experimental animals how macrophages, part of the immune system, can help repair the hearts of newborns and adults after a heart attack. The study highlights the fundamental differences in how the immune system drives healing according to age.
The study will be published in the journal Immunization on February 11.
“Understanding why newborns can regenerate their own hearts, and adults cannot open the door to developing treatments that can “reprogram” adult macrophages,” said Connor Lantz, lead author at BioInformatics Core at the Northwestern Comprehensive Transplantation Center. University of Feinberg Medical College.
In neonates, macrophages perform a process called adrenalisation, which recognizes and consumes dying cells. The study found that this process triggers the production of a bioactive lipid called a thrombane that signals nearby cardiomyocytes and enables the heart to regenerate damaged heart muscle. In adults, macrophages produce much less thrombane, resulting in weaker repair signals.
“By mimicking the effects of thrombanes, we can one day improve tissue repair after a heart attack in adults,” Landz said.
Study how it works
The study examined how the immune system responded to heart damage in mice of different ages, including newborn mice (one day) and adult mice (eight weeks old). The researchers found that due to increased expression of MERTK, macrophages’ ability to phagocytize dying cells in newborn mice was enhanced, and MERTK expression was increased, a receptor that recognizes dying cells. So when scientists block this key receptor, newborn mice lose the ability to regenerate their hearts, similar to adult hearts after a heart attack.
The study found that the phagocytosis of dying cells triggered a chemical chain reaction that produced a molecule called the potential box A2, which unexpectedly stimulated cardiomyocytes to reproduce and repair damage. In addition, nearby muscle heart cells in newborns need to respond to thrombon A2, which allows them to change their metabolism to support their growth and healing. But in adults, this process doesn’t work the same way – after injury, their macrophages do not produce enough thrombane A2, limiting their ability to regenerate heart tissue.
The paper is titled “Infectious cytokinesis in young age uses macrophage arachnoid acid metabolism for tissue regeneration.” Edward B. Thorp, professor of experimental pathology at Feinberg, is a corresponding study author.
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