New research provides insight into how certain neuronal systems regulate the amount of heart muscle cells.

After birth, human heart muscle cells stop growing, which can cause permanent damage to the heart later in life. This can cause a decrease in function and lead to heart failure. However, now, Johns Hopkins Medicine researchers claim they have discovered new evidence from mouse studies that manipulating specific nerve cells or the genes that regulate them could trigger the creation of new heart muscle cells and restore function to the heart after heart attacks and other heart-related disorders.

They claim that their research published in Science Advances Dec. 1 sheds fresh light on the role of neurons in controlling the number of heart muscle cell cells.

Nerve cells have long been recognized as being involved in regulating heart function, but their role and impact on heart development and their effect on muscle cell growth is not clear.

Our study was designed to investigate the function of sympathetic neurons on heart development after birth. What we found is that by manipulating them, there may be a huge potential to regulate the total amount of heart muscle cells even after birth.”

Emmanouil Tampakakis M.D. Assistant professor of medicine, Johns Hopkins University School of Medicine and the lead researcher of the study.

The sympathetic nervous system (SNS) is comprised of nerve cells, controls automatic processes in the body like digestion heart rate, digestion, and respiration. The SNS is often associated with “fight-or-flight” responses, the body’s general response to alarming, stressful or potentially dangerous situations.

The new study was conducted by the research team. They created a genetically modified mouse model that blocks sympathetic heart neurons during the development of mouse embryos. They then analyzed the mechanisms behind the proliferation of heart muscle cells through the first two weeks after birth.

What they discovered was a significant reduction in the activity of two genes — the period 1 and period 2 genes the period 1 and period 2 genesthat are already recognized as being responsible for controlling the circadian cycle. Researchers found that taking these two circadian genes from mouse embryos led to an increase in the size of the neonatal heart and an increase in cardiomyocytes (or heart muscle cells), by up to 10 percent. This suggested that the effect of sympathetic nerves on heart muscle cells could be caused by these two circadian or “clock” genes.

Clock genes are components of the circadian rhythm that regulates the body’s functions on a 24 hour cycle that is aligned to dark and daylight hours.

“Shortly after birth, mammals, including people and mice stop producing heart muscle cells. The heart, unlike other organs like the liver, can’t be rebuilt once it’s damaged, says Tampakakis. “We have demonstrated that it is possible to modify the circadian genes and the nerves, via treatments or drugs, in order to increase the number of heart cells after birth,” says Tampakakis.

Heart attacks can cause people to lose as many as one billion heart muscle cells. Tampakakis claims that the number of cells in the heart in the beginning is higher, which makes it more likely they will recover quicker. Researchers believe that the heart can be improved by manipulating the sympathetic nerves and the clock genes — a process known as neuromodulation.

“Neuromodulation is a pretty new concept in cardiology and we believe this is the first report that link clock genes to the growth of new heart muscle cells.” Chulan Kwon (M.S., Ph.D.) is associate professor of medicine at Johns Hopkins University School of Medicine and director of the Cardiovascular Stem Cell Program. “Our study demonstrates perhaps for the first time what happens when you cut the supply of nerves that the heart receives. It also provides new insights into the development of neuromodulation strategies to help the heart regenerate.

Tampakakis says his team is working on further studies to identify the various kinds of neurons that provide the heart and to demonstrate how the nerves develop and adjust as time passes and after heart injuries.

According to the U.S. Centers for Disease Control and Prevention Cardiovascular disease is the most frequent cause of death in the country leading to one death in four.
https://www.hopkinsmedicine.org/”>

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