Sympathetic Neurons Could Help Regulate Heart Cell Production

Johns Hopkins Medicine researchers have shared new evidence from mouse experiments that show how manipulating certain nerve cells—or the genes that control them—might trigger the formation of new heart muscle cells and restore heart function after heart attacks. More specifically, they say, their study published in Science Advances sheds new light on how some neurons regulate the number of heart muscle cells.

Nerve cells have long been known to regulate heart function, but their role and impact during heart development and their effect on muscle cell growth have been unclear. “Our study sought to examine the role of so-called sympathetic neurons on heart development after birth, and what we found is that by manipulating them, there could be tremendous potential for regulating the total number of muscle cells in the heart even after birth,” says Emmanouil Tampakakis, lead author of the study.  

For the new study, the research team created a genetically modified mouse model by blocking sympathetic heart neurons in developing mouse embryos and analyzed the drivers of heart muscle cell proliferation through the first two weeks of life after birth. What they found was a significant decrease in the activity of a pair of genes—the period 1 and period 2 genes—already known to control the circadian cycle. Remarkably, removing those two circadian genes in mouse embryos, the researchers saw increased neonatal heart size and an increase in the number of cardiomyocytes, or heart muscle cells, by up to 10%. This suggested that the effect of sympathetic nerves on heart muscle cells is likely mediated through these two circadian or “clock” genes.

“Shortly after birth, mammals, including people and mice, stop producing heart muscle cells. And unlike other organs, like the liver, the heart can’t regenerate after it’s damaged,” says Tampakakis. “We’ve shown that it may be possible to manipulate nerves and/or circadian genes, either through drugs or gene therapies, to increase the number of heart cells after birth.”