Hypertrophy Inducing Factor In Pediatric Idiopathic Dilated Cardiomyopathy Serum

Abstract

IntroductionHeart failure (HF) is a devastating and costly disease that results in about 50% mortality within 5 years of diagnosis. Despite improvements in adult HF outcomes, children with HF have had no substantial improvement in survival over the past 3 decades. Our work has shown that the myocardium of children with idiopathic dilated cardiomyopathy (IDC) demonstrates a gene expression pattern consistent with pathologic remodeling. The objective of this study was to investigate whether serum from pediatric IDC patients would recapitulate this pathologic gene expression pattern in neonatal rat ventricular myocytes (NRVMs).MethodsNRVMs were treated with: 1) whole serum from IDC and non‐failing (NF) control patients; 2) heat inactivated serum; or 3) exosomes isolated from serum. Serum protein identification was performed by mass spectrometry.ResultsTreatment of NRVMs with whole serum from pediatric IDC patients induced a pathologic hypertrophic response that was characterized by changes in gene expression and increase in cell size. These changes were prevented by heat inactivation, indicating a protein factor. Exosome treatment suggests that the observed effect is also mediated by RNAs/miRNAs.ConclusionWe show that circulating factors (RNA and protein) present in the serum of pediatric IDC patients but not in NF controls, induce a pathologic response in NRVMs. Identification of these circulating factors could represent a novel approach to age‐specific HF drug discovery.Source of Research Support: NIH‐NHLBI R01 HL107715 (BLS), APS Undergraduate Summer Research Fellowship (JSC)