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Comparison of the stage-dependent mitochondrial changes in response to pressure overload between the diseased right and left ventricle in the rat

  • Mitochondria at the heart of cardioprotection
  • Published:
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Abstract

The right ventricle (RV) differs developmentally, anatomically and functionally from the left ventricle (LV). Therefore, characteristics of LV adaptation to chronic pressure overload cannot easily be extrapolated to the RV. Mitochondrial abnormalities are considered a crucial contributor in heart failure (HF), but have never been compared directly between RV and LV tissues and cardiomyocytes. To identify ventricle-specific mitochondrial molecular and functional signatures, we established rat models with two slowly developing disease stages (compensated and decompensated) in response to pulmonary artery banding (PAB) or ascending aortic banding (AOB). Genome-wide transcriptomic and proteomic analyses were used to identify differentially expressed mitochondrial genes and proteins and were accompanied by a detailed characterization of mitochondrial function and morphology. Two clearly distinguishable disease stages, which culminated in a comparable systolic impairment of the respective ventricle, were observed. Mitochondrial respiration was similarly impaired at the decompensated stage, while respiratory chain activity or mitochondrial biogenesis were more severely deteriorated in the failing LV. Bioinformatics analyses of the RNA-seq. and proteomic data sets identified specifically deregulated mitochondrial components and pathways. Although the top regulated mitochondrial genes and proteins differed between the RV and LV, the overall changes in tissue and cardiomyocyte gene expression were highly similar. In conclusion, mitochondrial dysfuntion contributes to disease progression in right and left heart failure. Ventricle-specific differences in mitochondrial gene and protein expression are mostly related to the extent of observed changes, suggesting that despite developmental, anatomical and functional differences mitochondrial adaptations to chronic pressure overload are comparable in both ventricles.

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Data availability

The rat RNA-seq. data sets of this study have been submitted to GEO: GSE216264 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE216264). The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [38] partner repository with the dataset identifier PXD047022. The remaining supporting data of the present study are available in the article and its supplementary information.

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Acknowledgements

We appreciate the technical assistance of B. Reuter and S. Fiedler.

Funding

This work is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Projektnummer 268555672-SFB 1213, project B03 to S.R., M.L.S., M.K. and project B05 to R.S.) and by the FCMH Flexifunds to the Mitochondrial Network consortium (to S.R.). Work in the laboratory of M.K. is further supported by the IMPRS program of the Max Planck Society and the Excellence Cluster Cardio-Pulmonary Institute (EXC 2026: Cardio-Pulmonary Institute [CPI], project 390649896) and the DZL/UGMLC/ILH program.

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Author notes

  1. Ling Li, Bernd Niemann, Michael Kracht, and Susanne Rohrbach have contributed equally to this work.

Authors and Affiliations

  1. Institute of Physiology, Justus Liebig University Giessen, Aulweg 129, 35392, Giessen, Germany

    Ling Li, Fabienne Knapp, Nicole Molenda, Rainer Schulz & Susanne Rohrbach

  2. Department of Cardiac and Vascular Surgery, Justus Liebig University Giessen, Rudolf-Buchheim-Street. 8, 35392, Giessen, Germany

    Bernd Niemann

  3. Rudolf Buchheim Institute of Pharmacology, Justus Liebig University Giessen, Schubertstrasse 81, 35392, Giessen, Germany

    Sebastian Werner, Liane M. Jurida & Michael Kracht

  4. Hannover Medical School, Institute of Functional and Applied Anatomy, Carl-Neuberg-Street. 1, 30625, Hannover, Germany

    Christian Mühlfeld & Jan Philipp Schneider

  5. Institute of Biochemistry, Justus Liebig University Giessen, Friedrichstr. 24, 35392, Giessen, Germany

    M. Lienhard Schmitz

  6. School of Cardiovascular and Metabolic Medicine and Science, King’s College London, 125 Coldharbour Lane, London, SE5 9NU, UK

    Xiaoke Yin & Manuel Mayr

Authors
  1. Ling Li
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  2. Bernd Niemann
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Contributions

Conceptualization: Susanne Rohrbach, Michael Kracht, Bernd Niemann; Methodology: Bernd Niemann; Formal analysis and investigation: Ling Li, Fabienne Knapp, Liane M. Jurida, Sebastian Werner, Jan Philipp Schneider, Christian Mühlfeld, Xiaoke Yin, Nicole Molenda, Michael Kracht; Writing—original draft preparation: Susanne Rohrbach; Writing—review and editing: Rainer Schulz, Michael Kracht, Jan Philipp Schneider, Christian Mühlfeld; Funding acquisition: M. Lienhard Schmitz, Rainer Schulz, Michael Kracht, Susanne Rohrbach; Resources: Christian Mühlfeld; Manuel Mayr; Supervision: Michael Kracht, Susanne Rohrbach, Bernd Niemann; Visualization: Michael Kracht, Bernd Niemann, Susanne Rohrbach.

Corresponding author

Correspondence to Susanne Rohrbach.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The experimental protocols were approved by the regional authorities and ethics committees for animal research (RP Giessen) and conformed to the guidelines from Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes. The experiments were registered under the number G14-2017. We followed the ARRIVE guidelines 2.0 [37]. The manuscript does not contain clinical studies or patient data.

Additional information

This article is part of the special issue “Mitochondria at the heart of cardioprotection”.

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Li, L., Niemann, B., Knapp, F. et al. Comparison of the stage-dependent mitochondrial changes in response to pressure overload between the diseased right and left ventricle in the rat. Basic Res Cardiol (2024). https://doi.org/10.1007/s00395-024-01051-3

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  • DOI: https://doi.org/10.1007/s00395-024-01051-3

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