Mracek 2014 Abstract MiP2014
|Function of mitochondrial energy provision apparatus is compromised in patients with chronic heart failure. Mitochondr Physiol Network 19.13.|
Epidemic increase in the prevalence of heart failure is a common feature in all developed countries. Regardless of the underlying aetiology, defects in myocardial mitochondrial energetics play a central role in its pathogenesis, since the heart function places enormous demands on the range and dynamics of energy provision. Diminished functional capacity of mitochondria can, therefore, lead to heart failure [1, 2]. Our aim was to elucidate prevalence and significance of abnormalities of the mitochondrial energetic apparatus in the myocardium of patients with advanced heart failure, and to describe putative mechanisms leading to such abnormalities.
We analyzed left ventricular myocardial tissue of patients undergoing heart transplantation harvested at the time of the heart explanation (N=62) and samples of control myocardial tissue harvested from hearts of organ donors not used for cardiac transplantation (N=20). In the heart failure samples, we found profound markers of mitochondrial dysfunction. Content of mitochondria was decreased both when detected as mtDNA content (76% of controls) and citrate synthase activity (74% of controls). Similarly, we observed a decrease in activities of OXPHOS enzymes: NADH:cytochrome c oxidoreductase (NCCR) (122±5.7 vs. 161±13, P<0.01), succinate:cytochrome c oxidoreductase (SCCR) (66±4.7 vs. 111±7.9, P<0.001) and cytochrome c oxidase (472±18 vs. 767±56, P<0.001). Using high-resolution respirometry, we detected a decrease in succinate supported respiration (451±23 vs. 598±47, P<0.01). SDS electrophoresis showed a decrease in content of Complexes I, II and III and a significant decrease in the endonuclease G, a mitochondrial protein recently associated with heart failure. Concerning aetiology, no differences were observed between patients with ischemic (coronary arterial disease) and non-ischemic heart failure.
Taken together, our data implicate the important role of mitochondrial respiratory capacity in the development of human heart failure.
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Patients Pathology: Cardiovascular
Organism: Human Tissue;cell: Heart Preparation: Permeabilized tissue Enzyme: Complex IV;cytochrome c oxidase
Coupling state: OXPHOS Pathway: S HRR: Oxygraph-2k Event: C4, P-flash MiP2014
1-Dep Bioenergetics, Inst Physiol AS CR v.v.i.; 2-Inst Clinical Exp Medicine; 3- Dep Transplantation Tissue Banking, Univ Hospital Motol; Prague, Czech Republic. - firstname.lastname@example.org
References and acknowledgements
This work was supported by the Ministry of Health of the Czech Republic project no. NT14050.
- Lemieux H, Semsroth S, Antretter H, Höfer D, Gnaiger E (2011) Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart. Int J Biochem Cell Biol 43: 1729–38.
- Rosca MG, Hoppel CL (2013) Mitochondrial dysfunction in heart failure. Heart Fail Rev 5: 607-22.