Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2015 (2015), Article ID 424751, 14 pages
Research Article

Oxidative Stress in Dilated Cardiomyopathy Caused by MYBPC3 Mutation

1Department of Cell and Molecular Physiology, Health Sciences Division, Loyola University Chicago, Maywood, IL 60153, USA
2Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
3Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
4Department of Cardiology, Thoraxcenter, Erasmus Medical Center, ’s-Gravendijkwal 230, 3015 CE Rotterdam, Netherlands
5Bosch Institute, Discipline of Anatomy and Histology, University of Sydney, Sydney, NSW 2006, Australia
6Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, Netherlands

Received 15 January 2015; Revised 1 July 2015; Accepted 9 August 2015

Academic Editor: Felipe Dal Pizzol

Copyright © 2015 Thomas L. Lynch IV et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Cardiomyopathies can result from mutations in genes encoding sarcomere proteins including MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C). However, whether oxidative stress is augmented due to contractile dysfunction and cardiomyocyte damage in MYBPC3-mutated cardiomyopathies has not been elucidated. To determine whether oxidative stress markers were elevated in MYBPC3-mutated cardiomyopathies, a previously characterized 3-month-old mouse model of dilated cardiomyopathy (DCM) expressing a homozygous MYBPC3 mutation (cMyBP-) was used, compared to wild-type (WT) mice. Echocardiography confirmed decreased percentage of fractional shortening in DCM versus WT hearts. Histopathological analysis indicated a significant increase in myocardial disarray and fibrosis while the second harmonic generation imaging revealed disorganized sarcomeric structure and myocyte damage in DCM hearts when compared to WT hearts. Intriguingly, DCM mouse heart homogenates had decreased glutathione (GSH/GSSG) ratio and increased protein carbonyl and lipid malondialdehyde content compared to WT heart homogenates, consistent with elevated oxidative stress. Importantly, a similar result was observed in human cardiomyopathy heart homogenate samples. These results were further supported by reduced signals for mitochondrial semiquinone radicals and Fe-S clusters in DCM mouse hearts measured using electron paramagnetic resonance spectroscopy. In conclusion, we demonstrate elevated oxidative stress in MYPBC3-mutated DCM mice, which may exacerbate the development of heart failure.