Researchers at the University Hospital of Bonn (UKB) and the University of Bonn have identified a previously unknown signaling pathway in the immune system that helps newborn heart cells survive and regenerate after injury. The findings could open new avenues for future therapies aimed at repairing damaged adult hearts after heart attacks or chronic cardiovascular disease. The study has now been published in the journal Cell Communication and Signaling (Springer Nature).

Unlike adult hearts, the hearts of newborn mammals can temporarily regenerate after damage. However, this remarkable ability is rapidly lost within the first days of life. In the new study, scientists investigated how neonatal hearts respond both to heart injury and to pressure overload, a condition that mimics chronic stress on the heart.

Immune cells communicate via signaling pathways that function like a chain of dominoes. In this process, signaling molecules trigger the next signal until a reaction is initiated. In a neonatal mouse model, the research team discovered that three immune-related signaling molecules — CCL4, S100A8, and C1QA — work together to activate a receptor called TLR2 on heart muscle cells. Activation of this pathway stimulated heart cell proliferation, enhanced survival of heart muscle cells, and reduced cell death.

“Our findings reveal an unexpected communication axis between immune signals and heart muscle cells that supports regeneration in the neonatal heart,” said corresponding author Dr. Mona Malek Mohammadi, head of a research group at the Institute of Physiology I at the UKB and the University of Bonn. “We were particularly surprised to find that TLR2 acts as a central hub connecting inflammatory signals to regenerative responses.”

No signaling pathway—no heart repair

To validate the importance of TLR2, the researchers used genetically modified mice lacking the receptor. These mice were unable to adapt to cardiac stress and rapidly developed heart failure. “This shows that TLR2 is essential for maintaining protective and regenerative responses in the neonatal heart,” says the first author Julia Nicke.

Importantly, the study also showed that TLR2 expression is much higher in newborn heart cells than in adult heart cells, suggesting that loss of this signaling pathway may contribute to the poor regenerative capacity of the adult heart.

The researchers believe these findings may eventually help scientists develop therapies that reactivate neonatal-like repair mechanisms in adult hearts after myocardial infarction or heart failure. “Current cardiovascular therapies mainly slow disease progression,” said Dr. Malek Mohammadi. “Our long-term goal is to promote true cardiac repair and regeneration.”

Funding:
The study was conducted at the UKB and funded by the German Society of Cardiology (Deutsche Gesellschaft für Kardiologie, DGK) through a research grant awarded to Dr. Mona Malek Mohammadi.

Publication: Julia Nicke, Adrian Goldspink, Malte Menn, Bernd K. Fleischmann, Mona Malek Mohammadi: TLR2 mediates cell cycle re-entry and survival of neonatal cardiomyocytes in response to injury; Cell Communication and Signaling (Springer Nature); DOI: 10.1186/s12964-026-03147-w