Inefficient repair of the cardiac tissue following injury (infarction, stress, other) forms the common ground of
most severe cardiovascular conditions exemplified in deadly heart failure. Efficient therapeutic approaches
based on novel mediator and pathways discovery is an unmet and urgent need. Inflammation may promote
both fibrosis and cardiac regeneration. Among innate immune cells, myeloid subpopulations differentially
affect cardiac repair in the adult heart and may facilitate cardiomyocyte proliferation and regeneration in
neonatal mice and in the zebrafish. Importantly and in contrast to mice, zebrafish maintain the ability to
regenerate their hearts throughout life and, furthermore, they constitute a powerful vertebrate but non-
mammalian example, easy to monitor and to study successful cardiac disease and regeneration. Combining
these two extremities we propose here to analyze the myeloid arsenal of secreted mediators affecting cardiac
repair and regeneration. To do this we have developed and will expand a series of analytical tools that include
genetic modifications in both the zebrafish and the mouse, or their combination, and we propose to employ
them in order i) to characterize and establish novel, potentially druggable, mediators, and ii) to further
understand the contribution of innate immunity in cardiac repair.