Paulus 2022 Basic Res Cardiol

From Bioblast
Publications in the MiPMap
Paulus MG, Renner K, Nickel AG, Brochhausen C, Limm K, ZΓΌgner E, Baier MJ, Pabel S, Wallner S, Birner C, Luchner A, Magnes C, Oefner PJ, Stark KJ, Wagner S, Maack C, Maier LS, Streckfuss-BΓΆmeke K, Sossalla S, Dietl A (2022) Tachycardiomyopathy entails a dysfunctional pattern of interrelated mitochondrial functions.

Β» Basic Res Cardiol 117:45. PMID: 36068416 Open Access

Paulus Michael G, Renner Kathrin, Nickel Alexander G, Brochhausen Christoph, Limm Katharina, Zuegner Elmar, Baier Maria J, Pabel Steffen, Wallner Stefan, Birner Christoph, Luchner Andreas, Magnes Christoph, Oefner Peter J, Stark Klaus J, Wagner Stefan, Maack Christoph, Maier Lars S, Streckfuss-Boemeke Katrin, Sossalla Samuel, Dietl Alexander (2022) Basic Res Cardiol

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 Β± 1.0% vs. 21.9 Β± 1.2%, SHAM vs. TCM, p < 0.0001). Histology revealed cardiomyocyte hypertrophy (cross-sectional area 393.2 Β± 14.5 Β΅m2 vs. 538.9 Β± 23.8 Β΅m2, 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 Β± 2.1 vs. 4.0 Β± 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 Β± 11.2 vs. 124.6 Β± 11.45 pmolΒ·O2Β·s-1Β·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. β€’ Keywords: Acetylome, Mitochondria, Redox, Tachycardiomyopathy β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: DE Wuerzburg Maack C, DE Regensburg Renner-Sattler K

Labels: MiParea: Respiration  Pathology: Cardiovascular, Myopathy 

Organism: Rabbit  Tissue;cell: Heart  Preparation: Permeabilized tissue, Isolated mitochondria 

Coupling state: OXPHOS, ET  Pathway: F, NS, ROX  HRR: Oxygraph-2k 


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