Researchers at the Max Delbrück Center for Molecular Medicine (MDC) have uncovered a mechanism that enables zebrafish to completely restore heart muscle after a heart attack. This breakthrough could pave the way for new drugs that promote heart regeneration in humans. The findings were published in Developmental Cell.
Unlike humans, who form scar tissue after a heart attack that replaces damaged muscle and reduces the heart’s pumping ability, zebrafish can regenerate the myocardium. In a new study, scientists identified a signaling pathway that may trigger the growth of healthy heart tissue following injury, offering a potential blueprint for regenerative therapies in people.
It is known that the autonomic nervous system and the immune system—particularly macrophages—play pivotal roles in regeneration during cardiac injury. In this study, researchers used zebrafish larvae, which are transparent in early development, to observe the regeneration process in real time. The transparency makes it possible to track how heart cells respond to damage and how other bodily systems influence repair.
The team induced myocardial damage in zebrafish and selectively blocked several surface molecules on macrophages that are important for heart regeneration. By doing so, they mapped how the nervous system and the immune response communicate to drive tissue repair. When these molecules were blocked, macrophages failed to migrate to the injury site, heart muscle regeneration slowed or stalled, and scar formation began to predominate instead. The results point to a critical link between neural signals, immune cell behavior, and the restoration of heart tissue in this model organism. These experiments help explain why certain signals must be coordinated for repair to proceed effectively and how disruption of those signals can shift outcomes toward scarring. (attribution: MDC)
With these insights, scientists are now planning to compare how neural-to-immune signaling differs between zebrafish and humans. The goal is to learn why human heart tissue typically does not regenerate after injury and to identify the specific molecules that could serve as drug targets to spur regeneration in patients who have suffered a heart attack. A deeper understanding of this cross-talk could lead to therapies that promote myocardial regeneration, reduce scar tissue, and improve cardiac function in humans. (attribution: MDC)
Looking ahead, the research community will likely explore additional pathways and cellular players involved in cardiac repair, aiming to translate these discoveries into safe, effective treatments. The potential to convert a heart attack from a life-threatening event into a condition with restored heart muscle could transform cardiovascular care and patient outcomes, though researchers emphasize that translating findings from zebrafish to humans will require careful validation, optimization, and clinical testing. (attribution: MDC)
In summary, the study highlights a conserved and actionable interplay between neural signaling and immune cell activity that governs heart regeneration in a vertebrate model. By pinpointing the molecules that coordinate this interaction, the work sets the stage for developing regenerative strategies that could one day help human hearts heal more completely after injury.