Heart-brain neuroimmune triple-node in myocardial infarction
Arteries become clogged. Blood flow is restricted and oxygen is cut off. The result is a heart attack, the world’s leading cause of death.
The conventional approach to studying and treating these episodes is to focus on the heart as an isolated organ. The researchers are upending the way heart attacks are viewed under a transformative new understanding of how cardiac events are interconnected with other systems.
In a study published in the journal Cell, the researchers describe a comprehensive new picture of heart attacks and their resulting damage by connecting the heart, the brain and the nervous and immune systems.
Much like our eyes and ears convert light and sound from our environment into information the brain can understand and process, the new research reveals that a heart attack relays cardiovascular information to the brain via sensory neurons. The new research set out to unveil these connections. The new heart attack “maps” resulting from the study offer novel treatment opportunities under new perspectives of heart attacks as cross-connected systematic events, rather than isolated episodes.
“We believe this is the first comprehensive characterization of a “triple node” approach featuring a heart, brain and neuroimmune loop,” said the senior author. “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.”
When an injury or illness is detected, the brain responds by activating the immune system. A heart attack triggers a similar immune response. But while the brain considers a heart attack an injury, there are no pathogens or bacteria to defend against. This overactivation of the immune system likely worsens the damage.
Working in mice, the researchers found that sensory neurons in the vagus nerve first detect injury and transfer signals to dedicated brain structures, which in turn lead to activation of the immune system. Blocking the sensory and immune signals transmitting back and forth between the heart and the brain helped significantly reduce damage after a heart attack.
The researchers identified transient receptor potential vanilloid-1 (TRPV1)-expressing vagal sensory neurons (VSNs) that increase ventricular innervation post heart attack or myocardial infarction (MI). Ablating these VSNs mitigated MI pathology, reducing infarct size, abnormal electrocardiograms, cardiac dysfunction, sympathetic innervation, and pro-inflammatory cytokine interleukin 1β (IL-1β).
The authors found that MI activated angiotensin II receptor type 1 (AT1aR)-expressing neurons in the paraventricular nucleus (PVN), whose inhibition mirrored benefits of TRPV1 VSN ablation. In addition, the superior cervical ganglia (SCGs) exhibited intensified post-MI sympathetic innervation and IL-1β signaling. Blocking IL-1β in the SCG significantly reduced complications post MI.
While the researchers are still hoping to unravel the specific mechanisms involved, they believe new treatments for heart attacks could minimize the inadvertent damaging effects of the immune system following a heart attack episode.
“Blocking this heart-brain-neuroimmune system was shown to stop the spread of the disease,” said the lead author. “If you think of a heart attack as the epicenter, the blockage of the signals stopped the spread of the injury.”
According to the senior author, many of their findings have remained hidden because science is traditionally established in silos, with neuroscientists, cardiologists and immunologists concentrating in their own areas. Across four and a half years, the triple node discovery project brought neurobiologists together with scientists from the Departments of Medicine and Pediatrics (School of Medicine) and Shu Chien-Gene Lay Department of Bioengineering (Jacobs School of Engineering). In order to tease out the intricate connections involved, Yadav and his colleagues employed a variety of scientific techniques, including echocardiography, molecular staining, light sheet microscopy and ultrasound imaging to tease out the various linked pathways.
The resulting system maps underlying the three-node loop could help spur new treatments that address the interconnectedness of heart attacks.
“Current treatments for heart attacks focus on repairing the heart, including bypass surgery, angioplasty and blood thinners, which are all invasive,” said the senior author. “This research is showing that perhaps by manipulating the immune system we can drive a therapeutic response.”
https://www.cell.com/cell/fulltext/S0092-8674(25)01506-5
https://sciencemission.com/heart-brain-neuroimmune-loop
