The Role of Resident Embryonic-Derived Cardiac Macrophages in Ischemic Injury

Heart disease is the leading cause of mortality worldwide and macrophages (MFs) play a central role in both tissue healing and tissue injury. The precise origin and role of cardiac MFs in ischemic injury remains unknown, which could help explain the paradoxical role MFs seemingly play. Initial work in the lab suggested that adult bone marrow-derived MFs play a role in inducing inflammation, whereas resident embryonic-derived (EmbryoD) cardiac MFs promote repair. This thesis demonstrated that most cardiac MFs in steady state were EmbryoD and they persisted for the life of the animal. Following MI in adult animals, EmbryoD cardiac MFs were initially lost within the infarct and subsequently competed with recruited MFs within the heart. Specific chronic depletion of EmbryoD MFs post-MI resulted in depressed cardiac function and adverse cardiac remodeling in the vulnerable peri-infarct zone. The ability to increase the abundance of reparative EmbryoD cardiac MFs post-MI now represents a novel therapeutic approach.M.Sc