July 20, 2024

Heart Repair Enabled by Communication Between Nervous and Immune Systems: Study Finds

Zebrafish have the remarkable ability to fully regenerate their hearts after injury, a trait that humans lack. Researchers at the Max Delbrück Center, led by Suphansa Sawamiphak, have discovered that this regeneration is facilitated by the interaction between the fish’s nervous and immune systems. The findings, published in the journal Developmental Cell, shed light on the potential for heart repair in humans by targeting neuroimmune crosstalk.

Myocardial infarction, commonly known as a heart attack, affects over 300,000 people in Germany each year. While the survival rate has increased, the heart muscle damage caused by a heart attack is irreversible. Unlike zebrafish, which can grow new heart muscle cells, humans rely on fibroblasts to form scar tissue, leading to weaker heart pumping ability. Stem cell therapies, previously explored as a potential treatment for heart attack damage, have not yielded significant success.

Dr. Suphansa Sawamiphak and her team are taking a different approach to address heart repair. Recognizing the pivotal roles that the autonomic nervous system and immune system play in scarring and regeneration, Sawamiphak hypothesizes that communication between these systems determines the outcome after a heart attack. Macrophages, immune cells that play a role in both scarring and regeneration, are at the center of this decision-making process.

To investigate further, the researchers turned to zebrafish larvae for their study. These organisms are transparent, making it easier to visualize internal processes. Additionally, zebrafish can regenerate their hearts completely after injury, making them an ideal model for this research. The experimental approach involved inducing an injury similar to a heart attack in the larvae and blocking specific receptors on the surface of the macrophages. The results indicated that adrenergic signals from the autonomic nervous system determine the migration and proliferation of macrophages, as well as the regeneration of heart muscle tissue.

In subsequent experiments, genetically modified zebrafish were engineered to receive adrenergic signals but with interrupted transmission from the receptor to the cell’s interior. This highlighted the importance of signal transmission in heart regeneration. When the signal was blocked, scarring occurred instead of tissue regeneration.

The findings suggest that the crosstalk between the nervous and immune systems is a key regulator of heart repair. When macrophages are activated by the adrenergic signals, they communicate with fibroblasts, which facilitate regeneration by altering the extracellular matrix in the damaged area. This creates an environment conducive to the growth of blood and lymph vessels, promoting the development of new heart tissue. However, if the adrenergic signal is blocked, fibroblasts cause scarring, mirroring the process observed in human hearts after a heart attack.

The next step for the researchers is to examine the differences in signaling between zebrafish and humans in detail. This deeper understanding may reveal why heart muscle tissue fails to regenerate in humans. Furthermore, the team hopes to identify potential targets for intervention, affecting the neuroimmune interaction in a way that promotes heart tissue regeneration and maintains heart function in heart attack patients. These findings offer promising insights into the potential for future therapies focused on repairing damaged hearts.

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1. Source: Coherent Market Insights, Public sources, Desk research
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