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17-05-2024 | Heart Failure | Mitochondria at the heart of cardioprotection

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

Authors: Ling Li, Bernd Niemann, Fabienne Knapp, Sebastian Werner, Christian Mühlfeld, Jan Philipp Schneider, Liane M. Jurida, Nicole Molenda, M. Lienhard Schmitz, Xiaoke Yin, Manuel Mayr, Rainer Schulz, Michael Kracht, Susanne Rohrbach

Published in: Basic Research in Cardiology | Issue 4/2024

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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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Literature
2.
go back to reference Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Bohm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Pina IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CSP, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M (2021) Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 385:1451–1461. https://doi.org/10.1056/NEJMoa2107038CrossRefPubMed Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Bohm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Pina IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CSP, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M (2021) Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 385:1451–1461. https://​doi.​org/​10.​1056/​NEJMoa2107038CrossRefPubMed
8.
go back to reference Cung TT, Morel O, Cayla G, Rioufol G, Garcia-Dorado D, Angoulvant D, Bonnefoy-Cudraz E, Guerin P, Elbaz M, Delarche N, Coste P, Vanzetto G, Metge M, Aupetit JF, Jouve B, Motreff P, Tron C, Labeque JN, Steg PG, Cottin Y, Range G, Clerc J, Claeys MJ, Coussement P, Prunier F, Moulin F, Roth O, Belle L, Dubois P, Barragan P, Gilard M, Piot C, Colin P, De Poli F, Morice MC, Ider O, Dubois-Rande JL, Unterseeh T, Le Breton H, Beard T, Blanchard D, Grollier G, Malquarti V, Staat P, Sudre A, Elmer E, Hansson MJ, Bergerot C, Boussaha I, Jossan C, Derumeaux G, Mewton N, Ovize M (2015) Cyclosporine before PCI in patients with acute myocardial infarction. N Engl J Med 373:1021–1031. https://doi.org/10.1056/NEJMoa1505489CrossRefPubMed Cung TT, Morel O, Cayla G, Rioufol G, Garcia-Dorado D, Angoulvant D, Bonnefoy-Cudraz E, Guerin P, Elbaz M, Delarche N, Coste P, Vanzetto G, Metge M, Aupetit JF, Jouve B, Motreff P, Tron C, Labeque JN, Steg PG, Cottin Y, Range G, Clerc J, Claeys MJ, Coussement P, Prunier F, Moulin F, Roth O, Belle L, Dubois P, Barragan P, Gilard M, Piot C, Colin P, De Poli F, Morice MC, Ider O, Dubois-Rande JL, Unterseeh T, Le Breton H, Beard T, Blanchard D, Grollier G, Malquarti V, Staat P, Sudre A, Elmer E, Hansson MJ, Bergerot C, Boussaha I, Jossan C, Derumeaux G, Mewton N, Ovize M (2015) Cyclosporine before PCI in patients with acute myocardial infarction. N Engl J Med 373:1021–1031. https://​doi.​org/​10.​1056/​NEJMoa1505489CrossRefPubMed
9.
go back to reference Dirkx E, Gladka MM, Philippen LE, Armand AS, Kinet V, Leptidis S, El Azzouzi H, Salic K, Bourajjaj M, da Silva GJ, Olieslagers S, van der Nagel R, de Weger R, Bitsch N, Kisters N, Seyen S, Morikawa Y, Chanoine C, Heymans S, Volders PG, Thum T, Dimmeler S, Cserjesi P, Eschenhagen T, da Costa Martins PA, De Windt LJ (2013) Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure. Nat Cell Biol 15:1282–1293. https://doi.org/10.1038/ncb2866CrossRefPubMed Dirkx E, Gladka MM, Philippen LE, Armand AS, Kinet V, Leptidis S, El Azzouzi H, Salic K, Bourajjaj M, da Silva GJ, Olieslagers S, van der Nagel R, de Weger R, Bitsch N, Kisters N, Seyen S, Morikawa Y, Chanoine C, Heymans S, Volders PG, Thum T, Dimmeler S, Cserjesi P, Eschenhagen T, da Costa Martins PA, De Windt LJ (2013) Nfat and miR-25 cooperate to reactivate the transcription factor Hand2 in heart failure. Nat Cell Biol 15:1282–1293. https://​doi.​org/​10.​1038/​ncb2866CrossRefPubMed
12.
go back to reference Garcia-Lunar I, Jorge I, Saiz J, Solanes N, Dantas AP, Rodriguez-Arias JJ, Ascaso M, Galan-Arriola C, Jimenez FR, Sandoval E, Nuche J, Moran-Garrido M, Camafeita E, Rigol M, Sanchez-Gonzalez J, Fuster V, Vazquez J, Barbas C, Ibanez B, Pereda D, Garcia-Alvarez A (2024) Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation. Basic Res Cardiol. https://doi.org/10.1007/s00395-024-01041-5CrossRefPubMedPubMedCentral Garcia-Lunar I, Jorge I, Saiz J, Solanes N, Dantas AP, Rodriguez-Arias JJ, Ascaso M, Galan-Arriola C, Jimenez FR, Sandoval E, Nuche J, Moran-Garrido M, Camafeita E, Rigol M, Sanchez-Gonzalez J, Fuster V, Vazquez J, Barbas C, Ibanez B, Pereda D, Garcia-Alvarez A (2024) Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation. Basic Res Cardiol. https://​doi.​org/​10.​1007/​s00395-024-01041-5CrossRefPubMedPubMedCentral
13.
go back to reference Gomez-Arroyo J, Mizuno S, Szczepanek K, Van Tassell B, Natarajan R, dos Remedios CG, Drake JI, Farkas L, Kraskauskas D, Wijesinghe DS, Chalfant CE, Bigbee J, Abbate A, Lesnefsky EJ, Bogaard HJ, Voelkel NF (2013) Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension. Circ Heart Fail 6:136–144. https://doi.org/10.1161/CIRCHEARTFAILURE.111.966127CrossRefPubMed Gomez-Arroyo J, Mizuno S, Szczepanek K, Van Tassell B, Natarajan R, dos Remedios CG, Drake JI, Farkas L, Kraskauskas D, Wijesinghe DS, Chalfant CE, Bigbee J, Abbate A, Lesnefsky EJ, Bogaard HJ, Voelkel NF (2013) Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension. Circ Heart Fail 6:136–144. https://​doi.​org/​10.​1161/​CIRCHEARTFAILURE​.​111.​966127CrossRefPubMed
18.
35.
go back to reference Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Bohm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F (2020) Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 383:1413–1424. https://doi.org/10.1056/NEJMoa2022190CrossRefPubMed Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Bohm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F (2020) Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 383:1413–1424. https://​doi.​org/​10.​1056/​NEJMoa2022190CrossRefPubMed
36.
go back to reference Padron-Barthe L, Villalba-Orero M, Gomez-Salinero JM, Acin-Perez R, Cogliati S, Lopez-Olaneta M, Ortiz-Sanchez P, Bonzon-Kulichenko E, Vazquez J, Garcia-Pavia P, Rosenthal N, Enriquez JA, Lara-Pezzi E (2018) Activation of serine one-carbon metabolism by calcineurin abeta1 reduces myocardial hypertrophy and improves ventricular function. J Am Coll Cardiol 71:654–667. https://doi.org/10.1016/j.jacc.2017.11.067CrossRefPubMed Padron-Barthe L, Villalba-Orero M, Gomez-Salinero JM, Acin-Perez R, Cogliati S, Lopez-Olaneta M, Ortiz-Sanchez P, Bonzon-Kulichenko E, Vazquez J, Garcia-Pavia P, Rosenthal N, Enriquez JA, Lara-Pezzi E (2018) Activation of serine one-carbon metabolism by calcineurin abeta1 reduces myocardial hypertrophy and improves ventricular function. J Am Coll Cardiol 71:654–667. https://​doi.​org/​10.​1016/​j.​jacc.​2017.​11.​067CrossRefPubMed
37.
go back to reference Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, Garner P, Holgate ST, Howells DW, Karp NA, Lazic SE, Lidster K, MacCallum CJ, Macleod M, Pearl EJ, Petersen OH, Rawle F, Reynolds P, Rooney K, Sena ES, Silberberg SD, Steckler T, Wurbel H (2020) The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. J Physiol 598:3793–3801. https://doi.org/10.1113/JP280389CrossRefPubMed Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, Garner P, Holgate ST, Howells DW, Karp NA, Lazic SE, Lidster K, MacCallum CJ, Macleod M, Pearl EJ, Petersen OH, Rawle F, Reynolds P, Rooney K, Sena ES, Silberberg SD, Steckler T, Wurbel H (2020) The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. J Physiol 598:3793–3801. https://​doi.​org/​10.​1113/​JP280389CrossRefPubMed
38.
go back to reference Perez-Riverol Y, Bai J, Bandla C, Garcia-Seisdedos D, Hewapathirana S, Kamatchinathan S, Kundu DJ, Prakash A, Frericks-Zipper A, Eisenacher M, Walzer M, Wang S, Brazma A, Vizcaino JA (2022) The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res 50:D543–D552. https://doi.org/10.1093/nar/gkab1038CrossRefPubMed Perez-Riverol Y, Bai J, Bandla C, Garcia-Seisdedos D, Hewapathirana S, Kamatchinathan S, Kundu DJ, Prakash A, Frericks-Zipper A, Eisenacher M, Walzer M, Wang S, Brazma A, Vizcaino JA (2022) The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res 50:D543–D552. https://​doi.​org/​10.​1093/​nar/​gkab1038CrossRefPubMed
39.
go back to reference Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (esc). Developed with the special contribution of the heart failure association (HFA) of the ESC. Eur J Heart Fail 18:891–975. https://doi.org/10.1002/ejhf.592CrossRefPubMed Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P (2016) 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the european society of cardiology (esc). Developed with the special contribution of the heart failure association (HFA) of the ESC. Eur J Heart Fail 18:891–975. https://​doi.​org/​10.​1002/​ejhf.​592CrossRefPubMed
51.
go back to reference Singh S, Gaur A, Sharma RK, Kumari R, Prakash S, Kumari S, Chaudhary AD, Prasun P, Pant P, Hunkler H, Thum T, Jagavelu K, Bharati P, Hanif K, Chitkara P, Kumar S, Mitra K, Gupta SK (2023) Musashi-2 causes cardiac hypertrophy and heart failure by inducing mitochondrial dysfunction through destabilizing Cluh and Smyd1 mRNA. Basic Res Cardiol 118:46. https://doi.org/10.1007/s00395-023-01016-yCrossRefPubMed Singh S, Gaur A, Sharma RK, Kumari R, Prakash S, Kumari S, Chaudhary AD, Prasun P, Pant P, Hunkler H, Thum T, Jagavelu K, Bharati P, Hanif K, Chitkara P, Kumar S, Mitra K, Gupta SK (2023) Musashi-2 causes cardiac hypertrophy and heart failure by inducing mitochondrial dysfunction through destabilizing Cluh and Smyd1 mRNA. Basic Res Cardiol 118:46. https://​doi.​org/​10.​1007/​s00395-023-01016-yCrossRefPubMed
55.
61.
go back to reference Videira RF, Koop AMC, Ottaviani L, Poels EM, Kocken JMM, Dos Remedios C, Mendes-Ferreira P, Van De Kolk KW, Du Marchie Sarvaas GJ, Lourenco A, Llucia-Valldeperas A, Nascimento DA, De Windt LJ, De Man FS, Falcao-Pires I, Berger RMF, da Costa Martins PA (2022) The adult heart requires baseline expression of the transcription factor Hand2 to withstand right ventricular pressure overload. Cardiovasc Res 118:2688–2702. https://doi.org/10.1093/cvr/cvab299CrossRefPubMed Videira RF, Koop AMC, Ottaviani L, Poels EM, Kocken JMM, Dos Remedios C, Mendes-Ferreira P, Van De Kolk KW, Du Marchie Sarvaas GJ, Lourenco A, Llucia-Valldeperas A, Nascimento DA, De Windt LJ, De Man FS, Falcao-Pires I, Berger RMF, da Costa Martins PA (2022) The adult heart requires baseline expression of the transcription factor Hand2 to withstand right ventricular pressure overload. Cardiovasc Res 118:2688–2702. https://​doi.​org/​10.​1093/​cvr/​cvab299CrossRefPubMed
62.
go back to reference Wang J, Ma Z, Carr SA, Mertins P, Zhang H, Zhang Z, Chan DW, Ellis MJ, Townsend RR, Smith RD, McDermott JE, Chen X, Paulovich AG, Boja ES, Mesri M, Kinsinger CR, Rodriguez H, Rodland KD, Liebler DC, Zhang B (2017) Proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Mol Cell Proteom : MCP 16:121–134. https://doi.org/10.1074/mcp.M116.060301CrossRefPubMed Wang J, Ma Z, Carr SA, Mertins P, Zhang H, Zhang Z, Chan DW, Ellis MJ, Townsend RR, Smith RD, McDermott JE, Chen X, Paulovich AG, Boja ES, Mesri M, Kinsinger CR, Rodriguez H, Rodland KD, Liebler DC, Zhang B (2017) Proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Mol Cell Proteom : MCP 16:121–134. https://​doi.​org/​10.​1074/​mcp.​M116.​060301CrossRefPubMed
Metadata
Title
Comparison of the stage-dependent mitochondrial changes in response to pressure overload between the diseased right and left ventricle in the rat
Authors
Ling Li
Bernd Niemann
Fabienne Knapp
Sebastian Werner
Christian Mühlfeld
Jan Philipp Schneider
Liane M. Jurida
Nicole Molenda
M. Lienhard Schmitz
Xiaoke Yin
Manuel Mayr
Rainer Schulz
Michael Kracht
Susanne Rohrbach
Publication date
17-05-2024
Publisher
Springer Berlin Heidelberg
Keyword
Heart Failure
Published in
Basic Research in Cardiology / Issue 4/2024
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI
https://doi.org/10.1007/s00395-024-01051-3

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