Funded Research

Opposing Roles For Embryonic And Bone Marrow-Derived Macrophages In Pediatric Dilated Cardiomyopathy
Principal Investigator(s):
  • Kory Lavine, M.D., Ph.D. Medicine
Status:
Completed
Center(s):
  • Congenital Heart Disease Center
Award Mechanism:
Interdisciplinary Research Initiative
Project Period:
2/1/2015 - 1/31/2017
Total Amount:
$100,000
Background

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.

Specific aims

· 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

pediatric DCM.

· 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.