Abstract 20609: Abnormalities of Mitochondrial Number and Function in Pediatric Idiopathic Dilated Cardiomyopathy
Introduction: Impaired mitochondrial energy production and substrate utilization have been implicated in the development of heart failure (HF) in adults. Little literature exists describing mitochondrial energetics in pediatric HF. We have previously shown that content of Cardiolipin (CL), a major mitochondrial membrane phospholipid, is depleted in both adult and pediatric idiopathic dilated cardiomyopathy (IDC), with preserved expression of mitochondrial-encodes genes. Similar CL changes occur in a rat model of HF with associated mitochondrial dysfunction that precedes myocardial dysfunction, which can be reversed by dietary interventions.
Hypothesis: We hypothesize that mitochondrial dysfunction occurs in pediatric IDC.
Methods: As a part of an on-going study a cross-sectional analysis of mitochondrial content and function was performed in left ventricle tissue from the University of Colorado Pediatric Heart Tissue Bank. Current contents: age 13-18: 11 IDC (64% male) and 13 NF (62% male). All NF are donor hearts with normal LVEF; all IDC specimens had LVEF <30%.
Results: We show lower mitochondrial copy number in pediatric IDC compared with NF controls (IDC: 44 vs NF: 24, P<0.05), with paradoxical up-regulation of transcriptional co-activators, PGC1α and NRF1 (P<0.01). This is in contrast to what has been shown in adult HF where PGC1α and NRF1 expression are unchanged. Electron transport chain (ETC) complex enzymatic activities were quantified in a sub-group of pediatric IDC samples, expressed as Z-scores relative to normative values in 18 NFs. Significantly decreased activities of complexes I, IV, and citrate synthase were found (Z-scores -2.2, -3.3 and -1.7 respectively), with a significant increase in complex III activity (Z-score 0.7, all P<0.05).
Conclusions: These results suggest impaired mitochondrial biogenesis occurs in pediatric HF by a unique mechanism from that seen in adults. Additionally, we show a very specific pattern of ETC dysfunction in pediatric IDC. Future studies will identify the how decreased mitochondrial copy number occurs in the context of PGC1α and NRF1 up-regulation and determine whether abnormalities in CL contribute to abnormalities in ETC activities.
- Pediatric cardiology
- Mitochondrial energetics, heart failure, arrhythmias
- Heart failure
Author Disclosures: K.C. Chatfield: None. M.W. Friederich: None. S.D. Miyamoto: None. C.C. Sucharov: None. J.L. Van Hove: None. B.L. Stauffer: None.
- © 2014 by American Heart Association, Inc.