Christiansen 2015 Am J Physiol Heart Circ Physiol

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Publications in the MiPMap
Christiansen LB, Dela F, Koch J, Hansen CN, Leifsson PS, Yokota T (2015) Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy. Am J Physiol Heart Circ Physiol 308:H1237-47.

Β» PMID:25770243

Christiansen LB, Dela F, Koch J, Hansen CN, Leifsson PS, Yokota T (2015) Am J Physiol Heart Circ Physiol

Abstract: Mitochondrial dysfunction and oxidative stress are important players in the development of various cardiovascular diseases, but their roles in hypertrophic cardiomyopathy (HCM) remain unknown. We examined whether mitochondrial oxidative phosphorylation (OXPHOS) capacity was impaired with enhanced mitochondrial oxidative stress in HCM. Cardiac and skeletal muscles were obtained from nine domestic cats with spontaneously occurring HCM with preserved left ventricular systolic function and from 15 age-matched control cats. Mitochondrial OXPHOS capacities with non-fatty-acid and fatty-acid substrates in permeabilized fibers and isolated mitochondria were assessed by using high-resolution respirometry. Reactive oxygen species (ROS) release originating from isolated mitochondria was assessed by spectrofluorometry. Thiobarbituric acid reactive substances (TBARS) were also measured as a marker of oxidative damage. Mitochondrial ADP-stimulated state 3 respiration with complex I-linked non-fatty-acid substrates and with fatty-acid substrates, respectively, was significantly lower in the heart of HCM cats compared with control cats. Mitochondrial ROS release during state 3 with complex I-linked substrates and TBARS in the heart were significantly increased in cats with HCM. In contrast, there were no significant differences in mitochondrial OXPHOS capacity, mitochondrial ROS release, and oxidative damage in the skeletal muscle between groups. Mitochondrial OXPHOS capacity with both non-fatty-acid substrates and fatty-acid substrates was impaired with increased mitochondrial ROS release in the feline HCM heart. These findings provide new insight into the pathophysiology of HCM and support the hypothesis that restoration of the redox-state in the mitochondria is beneficial in the treatment of HCM. β€’ Keywords: Hypertrophic cardiomyopathy, Mitochondria, Oxidative stress, Amplex Red

β€’ O2k-Network Lab: DK Copenhagen Dela F, JP Sapporo Yokota T, DK Copenhagen Christiansen M, DK Copenhagen Larsen S, DK Copenhagen Larsen S

Labels: MiParea: Respiration, mt-Medicine, Patients  Pathology: Cardiovascular  Stress:Oxidative stress;RONS  Organism: Cat  Tissue;cell: Heart, Skeletal muscle  Preparation: Permeabilized tissue, Isolated mitochondria 

Regulation: Substrate, Fatty acid  Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, CIV, NS, ROX  HRR: Oxygraph-2k 


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