Abstract Body: Introduction: Our lab has previously demonstrated that mice treated with recombinant Interleukin-13 (IL13) post myocardial infarction (MI) demonstrate improved cardiac function through IL13 directly signaling to macrophages. While treatment with IL13 improves heart function, it has no effect on cardiac fibrosis post MI. Macrophages respond to IL13 through a receptor comprised of IL-4Rα and IL13Ra1. Paradoxically, when IL-4Rα is knocked out from macrophages, treatment with IL13 post MI no longer improves cardiac function but instead increases scar area of the heart by almost 50% compared to vehicle control. This suggests that IL13 is also signaling to myofibroblasts to promote fibrosis and that macrophages are suppressing this activity.

Hypothesis: We hypothesize that IL13 directly signals to cardiac myofibroblasts to aggravate scarring, as these cells express the IL13 receptor and largely contribute to fibrotic scarring in the post MI setting.

Methods: To test this hypothesis, we are utilizing a Cre-lox system to knock out IL-4Rα from myofibroblasts and macrophages in mice and then subject mice to MI and IL13 administration. Scar size and heart function are assessed over a 28-day period following MI. We’ve compared this double knockout genotype to mice that only have IL-4Rα knocked out of myofibroblasts, mice that only have IL-4Rα knocked out of macrophages, and wildtype control mice.

Results: Our data shows that when IL-4Rα is knocked out of both myofibroblasts and macrophages, treatment with IL13 results in less fibrosis compared to the macrophage IL-4Rα knockout group.

Conclusion: Our data suggests that, knocking out the IL-4Rα receptor from both myofibroblasts and macrophages indeed rescues the scar phenotype. Findings from this study will lead to novel mechanisms by which macrophages interact with cardiac cell types to influence post MI healing.