Targeting specific vagus nerve cells reduced heart damage in mice
After a heart attack, the heart “talks” to the brain. And this conversation could make recovery worse.
Shutting down nerve cells that send messages from injured heart cells to the brain improved the heart’s ability to pump and reduced scarring, according to experiments in mice. Target inflammation in a part of the nervous system where these “damage” messages are also found improved heart function and tissue repairthe scientists report on January 27 in Cell.
“This research is another great example that shows that we cannot consider an organ and its disease in isolation“, says Wolfram Poller, an interventional cardiologist at Massachusetts General Hospital and Harvard Medical School, who was not involved in the study. “And this opens the door to new therapeutic strategies and targets that go beyond the heart.”
In the United States, someone has a heart attack about every 40 seconds, according to the U.S. Centers for Disease Control and Prevention. This represents approximately 805,000 people each year.
A heart attack is a mechanical problem caused by blockage of a coronary artery, usually by a blood clot. If the blockage lasts long enough, affected cells may begin to die. Heart attacks can have long-term effects, such as a weakened heart, reduced ability to pump blood, irregular heart rhythms, and a higher risk of heart failure or another heart attack.
Although experts knew from previous research that the nervous and immune systems could amplify inflammation and slow healing, the key players and pathways involved were unknown, says Vineet Augustine, a neurobiologist at the University of California, San Diego.
To identify them, Augustine and his colleagues began by identifying the sensory neurons that detect damage to heart tissue. The team focused on vagus nervewhich carries sensory information from internal organs to the brain and identified a specific subtype of vagal sensory neurons, called TRPV-1-positive neurons, that extend into heart tissue and lie adjacent as key contributors to the brain-heart pathway. After a heart attack, more TRPV-1-positive nerve endings became active in the damaged area of the heart, experiments showed.
But when these neurons were shut down, heart pumping function, electrical stability scar size and other measures of heart health improved. This adds to the evidence that the heart speeds up the signals it sends to the brain after a heart attack.
The team traced the path of these signals from the heart to the brain. Their first stop was the paraventricular nucleus of the hypothalamus, a region that helps control stress, blood pressure and heart rate. The signals then reached the superior cervical ganglion, a group of nerve cells in the neck that send signals to organs such as the heart and blood vessels.
After a heart attack, the cluster of nerve cells in the neck appeared more inflamed, with high levels of pro-inflammatory molecules called cytokines. When scientists reduced inflammation in this group of nerve cells, heart damage lessened, and the team saw improvements in heart function and tissue repair.
It’s important to note that “the inflammatory response is not inherently negative,” says Tania Zaglia, a physiologist at the University of Padua in Italy who was not involved in the study. “In the early phases of the infarction, it is essential for the elimination of damaged tissues and for the activation of reparative processes.” However, she says, problems arise when this response becomes excessive, prolonged or disorganized.
That’s why controlling inflammation, as well as the nerves that can cause it, could be beneficial, researchers say. It will take time to bring the results from the mice to the clinic. Still, “we can now start to think about therapies such as vagus nerve stimulation, gene-based approaches targeting the brain, or treatments targeting the immune system,” Augustine says.
