Scientists uncover key mechanism in zebrafish heart regeneration

Zebrafish possess a remarkable ability to fully regenerate their hearts after injury, a feat beyond the reach of the human heart. Unlike our hearts, zebrafish hearts can recover due to the intricate interplay between their nervous and immune systems, according to research led by Dr. Suphansa Sawamiphak from the Max Delbrück Center.

In contrast, human hearts, damaged by myocardial infarction or heart attacks, suffer irreversible harm. Stem cell treatments, intended to repair infarction-damaged hearts, have proven largely unsuccessful. The human heart, lacking the capability to grow new muscle cells, relies on fibroblasts that form scar tissue, weakening its pumping power.

Dr. Sawamiphak’s team explores a novel approach, focusing on the communication between the autonomic nervous and immune systems. This communication, influenced by signals from the autonomic nervous system, determines whether scarring or regeneration occurs in the damaged heart muscle. Macrophages, known to play a role in both processes, become a focal point in this decision-making.

To unravel this mystery, researchers turn to zebrafish larvae for their unique regenerative abilities and optical transparency. By inducing heart injuries in these larvae and manipulating macrophage receptors, the team discovers that adrenergic signals dictate whether macrophages contribute to scarring or regeneration. The interruption of these signals triggers scarring, mirroring the human heart’s response to a heart attack.

Genetically modified zebrafish further reveal the importance of signal transmission in heart regeneration. If the adrenergic signal reaches macrophages but fails to transmit into the cell’s interior, scarring ensues. This insight becomes a key regulator in the cross-talk between nervous and immune systems. Activated macrophages, influenced by adrenergic signals, communicate with fibroblasts, paving the way for either regeneration or scarring.

As the research progresses, the team aims to dissect the signaling differences between zebrafish and humans. Understanding these distinctions could unveil why human heart tissue struggles to regenerate. Ultimately, the researchers aspire to identify potential targets for intervention, aiming to enhance the interaction between nervous and immune systems in a way that fosters heart muscle regeneration and preserves function in heart attack patients.

Source: Max Delbrück Center for Molecular Medicine

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