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Substrate-specific impairment of mitochondrial respiration in permeabilized fibers from patients with coronary heart disease versus valvular disease

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Abstract

High-resolution respirometry of permeabilized myocardial fibers offers reliable insights concerning the integrated mitochondrial function while using small amounts of cardiac tissue. The aim of the present study was to assess the respiratory function in permeabilized fibers of human right atrial appendages harvested from patients with coronary heart disease (CHD) (n = 6) versus patients with valvular disease (n = 5) and preserved ejection fraction that underwent non-emergency cardiac surgery. Human bundle samples (1–3 mg wet weight) permeabilized with saponin were transferred into the 2 ml Oxygraph-2 k chambers to measure complex I(CI) and II (CII)-dependent respiration, respectively. The following values (expressed in pmol/s mg) were obtained for CI-dependent respiration: oxidative phosphorylation (OXPHOS), 35.65 ± 1.10 versus 42.43 ± 1.08, electron transport system (ETS), 37.87 ± 1.72 versus. 46.58 ± 1.85, and respiratory control ratio (RCR, calculated as the ratio between OXPHOS and LEAK states), 2.43 ± 0.09 versus 2.73 ± 0.068 (p < 0.05). In conclusion, in patients with CHD we showed a significant decline for the OXPHOS capacity, ETS and RCR for mitochondria energized with CI (but not with CII) substrates. These observations are suggestive for an early impairment of complex I supported respiration in ischemic heart disease, as previously demonstrated in the setting of experimental ischemia/reperfusion in several animal species.

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Acknowledgments

O.D. gratefully acknowledge the support of COST action FA0602 allowing her to gather specific skills in high-resolution respirometry through the STSM FA0602-06082. This study was supported by the HU-RO/0901/137/2.2.2 project and the PhD fellowship POSDRU 1.5/88/S/ID 63117.

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Authors and Affiliations

  1. Department of Pathophysiology, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania

    Oana Duicu, Silvia Mirică, Ovidiu Firă-Mladinescu & Danina Muntean

  2. Institute of Cardiovascular Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania

    Călin Juşcă, Lucian Falniţă & Daniela Maximov

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  1. Oana Duicu
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Correspondence to Danina Muntean.

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Duicu, O., Juşcă, C., Falniţă, L. et al. Substrate-specific impairment of mitochondrial respiration in permeabilized fibers from patients with coronary heart disease versus valvular disease. Mol Cell Biochem 379, 229–234 (2013). https://doi.org/10.1007/s11010-013-1644-4

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