Paulus, Michael G. and Renner, Kathrin and Nickel, Alexander G. and Brochhausen, Christoph and Limm, Katharina and Zugner, Elmar and Baier, Maria J. and Pabel, Steffen and Wallner, Stefan and Birner, Christoph and Luchner, Andreas and Magnes, Christoph and Oefner, Peter J. and Stark, Klaus J. and Wagner, Stefan and Maack, Christoph and Maier, Lars S. and Streckfuss-Bomeke, Katrin and Sossalla, Samuel and Dietl, Alexander (2022) Tachycardiomyopathy entails a dysfunctional pattern of interrelated mitochondrial functions. BASIC RESEARCH IN CARDIOLOGY, 117 (1): 45. ISSN 0300-8428, 1435-1803
Full text not available from this repository. (Request a copy)Abstract
Tachycardiomyopathy is characterised by reversible left ventricular dysfunction, provoked by rapid ventricular rate. While the knowledge of mitochondria advanced in most cardiomyopathies, mitochondrial functions await elucidation in tachycardiomyopathy. Pacemakers were implanted in 61 rabbits. Tachypacing was performed with 330 bpm for 10 days (n = 11, early left ventricular dysfunction) or with up to 380 bpm over 30 days (n = 24, tachycardiomyopathy, TCM). In n = 26, pacemakers remained inactive (SHAM). Left ventricular tissue was subjected to respirometry, metabolomics and acetylomics. Results were assessed for translational relevance using a human-based model: induced pluripotent stem cell derived cardiomyocytes underwent field stimulation for 7 days (TACH-iPSC-CM). TCM animals showed systolic dysfunction compared to SHAM (fractional shortening 37.8 +/- 1.0% vs. 21.9 +/- 1.2%, SHAM vs. TCM, p < 0.0001). Histology revealed cardiomyocyte hypertrophy (cross-sectional area 393.2 +/- 14.5 mu m(2) vs. 538.9 +/- 23.8 mu m(2), p < 0.001) without fibrosis. Mitochondria were shifted to the intercalated discs and enlarged. Mitochondrial membrane potential remained stable in TCM. The metabolite profiles of ELVD and TCM were characterised by profound depletion of tricarboxylic acid cycle intermediates. Redox balance was shifted towards a more oxidised state (ratio of reduced to oxidised nicotinamide adenine dinucleotide 10.5 +/- 2.1 vs. 4.0 +/- 0.8, p < 0.01). The mitochondrial acetylome remained largely unchanged. Neither TCM nor TACH-iPSC-CM showed relevantly increased levels of reactive oxygen species. Oxidative phosphorylation capacity of TCM decreased modestly in skinned fibres (168.9 +/- 11.2 vs. 124.6 +/- 11.45 pmol center dot O-2 center dot s(-1)center dot mg(-1) tissue, p < 0.05), but it did not in isolated mitochondria. The pattern of mitochondrial dysfunctions detected in two models of tachycardiomyopathy diverges from previously published characteristic signs of other heart failure aetiologies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEART-FAILURE; OXIDATIVE STRESS; METABOLOMIC ANALYSIS; MYOCARDIAL FIBROSIS; ATRIAL-FIBRILLATION; CATHETER ABLATION; COMPLEX I; CALCIUM; TRANSHYDROGENASE; HYPERTROPHY; Tachycardiomyopathy; Mitochondria; Redox; Acetylome |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Innere Medizin II Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Lehrstuhl für Pathologie Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Dec 2023 07:30 |
| Last Modified: | 05 Dec 2023 07:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/56857 |
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