Abstract 416: Pluripotent Stem Cell Signaling in Pediatric Heart Failure Patients

Abstract

Pediatric heart failure is a heterogeneous disease process with congenital heart disease being the most common indication for heart transplantation in infants, and dilated cardiomyopathy (DCM) the most common indication in older children. Due to limitations of studying pediatric populations, there is no specific therapy for children with DCM. Importantly, the application of proven adult therapies to pediatric patients with DCM has resulted in no substantial improvement in survival over the past three decades. Therefore, there is a clear need for new approaches to better understand this disease process. In this study, we investigated global cardiac transcriptome and circulating serum proteome changes in pediatric patients with idiopathic dilated cardiomyopathy (IDC) and non-failing controls. Changes were identified in cytokine signaling, signal transduction, and transcription in pediatric IDC patients when compared to non-failing controls. Interestingly, these changes closely resemble the induction of stem cell pluripotency and signaling in resting stem cell populations. Importantly, the transcriptome changes are age-specific and were not observed in adult IDC patients. In addition, the protein profile in serum from pediatric IDC patients identified several factors related to inflammation, and treatment of cardiomyocyte-derived induced pluripotent stem cells (iPSC) with pediatric IDC serum recapitulated pathologic changes in gene expression, including expression of genes altered in the failing pediatric heart. These findings suggest that pathologic changes in cardiomyocytes may be triggered by circulating factors present in the serum resulting in pluripotent and stem cell signaling. These results provide several novel targets for future research and therapeutic intervention.