UC San Diego researchers have uncovered a three-way loop connecting the heart, brain and immune system during heart attacks. The discovery could lead to new, less invasive treatments that limit damage after a cardiac event.
Arteries clog, blood flow slows, oxygen is cut off — and a heart attack begins. For decades, doctors and scientists have largely treated that crisis as a problem contained within the heart itself.
New research from the University of California San Diego is challenging that view, revealing that heart attacks are deeply intertwined with the brain and the body’s immune defenses. The work opens the door to future treatments that may protect patients not just by repairing the heart, but by calming harmful signals that ripple through the nervous and immune systems.
In a study published in the journal Cell, a team led by UC San Diego School of Biological Sciences describes a three-way communication loop that activates when a heart attack strikes. Working in mice, the scientists traced how sensory nerves detect cardiac injury, relay that information to specific brain regions, and trigger an immune response that can unintentionally worsen damage to heart tissue.
The researchers call this a heart-brain-neuroimmune loop, and they argue that understanding it could transform how medicine thinks about heart attacks.
“We believe this is the first comprehensive characterization of a “triple node” approach featuring a heart, brain and neuroimmune loop,” co-corresponding author Vineet Augustine, an assistant professor in the Department of Neurobiology, said in a news release. “Heart attacks are obviously centered in the heart, but we’re flipping the switch on heart attack research to show that it’s not just the heart itself that is involved.”
The study focuses on the vagus nerve, a major communication highway that runs between the brain and many organs, including the heart. Sensory neurons in this nerve act a bit like the eyes and ears of the cardiovascular system, detecting changes and sending signals to the brain.
The UC San Diego team found that when a heart attack occurs, these sensory neurons pick up signs of injury and transmit them to dedicated brain structures. The brain, in turn, responds as if the body has been wounded or infected, calling in the immune system.
Under normal circumstances, that immune response helps fight off pathogens and clear away damaged cells. But in the case of a heart attack, there are no bacteria or viruses to battle. Instead, the overactive immune response can inflame and injure already stressed heart tissue.
To probe this process, the scientists used a suite of advanced tools, including echocardiography, molecular staining, light sheet microscopy and ultrasound imaging. These methods allowed them to visualize and track the pathways linking the heart, the vagus nerve, the brain and immune cells over time.
From this work, they built detailed system “maps” of the three-node loop. These maps show how information flows from the injured heart to the brain and back out to the immune system, and how that loop can amplify damage.
The team then tested what would happen if they interrupted that communication. By blocking sensory and immune signals traveling between the heart and brain in mice, they were able to significantly reduce the spread of damage after a heart attack.
Interfering with the loop changed the course of disease, according to co-first author Saurabh Yadav, a postdoctoral scholar in the Augustine lab.
“Blocking this heart-brain-neuroimmune system was shown to stop the spread of the disease,” Yadhav said in the news release. “If you think of a heart attack as the epicenter, the blockage of the signals stopped the spread of the injury.”
The findings suggest that future therapies might not need to act directly on the heart muscle to make a difference. Instead, they could aim to fine-tune the immune response that follows a heart attack, preventing the body from overshooting and harming itself.
Today’s standard treatments for heart attacks focus on restoring blood flow and repairing or bypassing blocked arteries. These include emergency procedures such as angioplasty and bypass surgery, along with long-term use of blood thinners and other drugs.
Augustine noted that these approaches, while lifesaving, can be demanding on patients.
“Current treatments for heart attacks focus on repairing the heart, including bypass surgery, angioplasty and blood thinners, which are all invasive,” he said. “This research is showing that perhaps by manipulating the immune system we can drive a therapeutic response.”
The work also highlights how scientific silos can hide important connections. The project unfolded over more than four years and brought together neurobiologists, cardiologists, immunologists and bioengineers from across UC San Diego, including the School of Medicine and the Jacobs School of Engineering.
By combining expertise and technologies from these different fields, the team was able to see the heart attack not just as a local event in one organ, but as a whole-body crisis involving multiple systems.
The study was conducted in animals, so any new therapies based on this concept are still years away. Researchers in Augustine’s lab are now working to unravel the precise molecular mechanisms that drive the heart-brain-neuroimmune loop and to identify specific targets that might be safely adjusted in people.
Still, the idea that doctors might one day protect heart attack patients by dialing down damaging immune signals — rather than only opening arteries and patching up the heart — is a powerful one.
If successful, such treatments could mean fewer complications, less long-term damage and better recoveries for millions of people worldwide who face heart attacks each year.