Pediatric dilated cardiomyopathy (DCM) is an important cause of mortality and is the most common indication for heart transplantation in children. Unfortunately, outcomes for patients with pediatric DCM remain poor and no effective therapies are available. These findings highlight the unmet need to identify novel therapies for patients with DCM, a core mission of the CDI.
We previously demonstrated that distinct reparative (CCR2-) and inflammatory (CCR2+) macrophage
populations contribute to cardiac repair and heart failure progression, respectively. Based on these findings, we propose that manipulation of cardiac macrophage subsets may alter the pathogenesis of pediatric DCM.
· Test the hypothesis that CCR2- macrophages are beneficial in the context of pediatric DCM by
stimulating tissue repair.
· Test the hypothesis that CCR2+ macrophages are inflammatory and negatively impact outcomes in
· Test the hypothesis that CCR2- macrophages derived from either embryonic or monocyte progenitors
have similar functions.
Describe the potential impact on child health
These studies will provide novel insights into pediatric DCM pathogenesis and test whether manipulation of macrophage composition could serve as a therapeutic target to delay heart failure progression and/or promote cardiac recovery.