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Revealing tissue-specific metabolic crosstalk after a myocardial infarction

Muhammad Arif, Martina Klevstig, Rui Benfeitas, Stephen Doran, Hasan Turkez, Mathias Uhlén, Maryam Clausen, Johannes Wikström, Damla Etal, Cheng Zhang, Malin Levin, Adil Mardinoglu, Jan Boren
doi: https://doi.org/10.1101/2020.10.28.358556
Muhammad Arif
1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
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Martina Klevstig
2Department of Molecular and Clinical Medicine, University of Gothenburg, The Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden
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Rui Benfeitas
3National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, S-10691 Stockholm, Sweden
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Stephen Doran
4Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT, United Kingdom
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Hasan Turkez
5Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum, 25240, Turkey
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Mathias Uhlén
1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
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Maryam Clausen
6Translational Genomics, BioPharmaceuticals R&D, Discovery Sciences, AstraZeneca, Gothenburg, Sweden
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Johannes Wikström
7Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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Damla Etal
6Translational Genomics, BioPharmaceuticals R&D, Discovery Sciences, AstraZeneca, Gothenburg, Sweden
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Cheng Zhang
1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
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Malin Levin
2Department of Molecular and Clinical Medicine, University of Gothenburg, The Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden
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Adil Mardinoglu
1Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden
4Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT, United Kingdom
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  • For correspondence: adilm@scilifelab.se Jan.Boren@wlab.gu.se
Jan Boren
2Department of Molecular and Clinical Medicine, University of Gothenburg, The Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden
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  • For correspondence: adilm@scilifelab.se Jan.Boren@wlab.gu.se
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Abstract/Summary

Myocardial infarction (MI) promotes a range of systemic effects, many of which are unknown. Here, we investigated the alterations associated with MI progression in heart and other metabolically active tissues (liver, skeletal muscle, and adipose) in a mouse model of MI (induced by ligating the left ascending coronary artery) and sham-operated mice. We performed a genome-wide transcriptomic analysis on tissue samples obtained 6- and 24-hours post MI or sham operation. By generating tissue-specific biological networks, we observed: (1) dysregulation in multiple biological processes (including immune system, mitochondrial dysfunction, fatty-acid beta-oxidation, and RNA and protein processing) across multiple tissues post MI; and (2) tissue-specific dysregulation in biological processes in liver and heart post MI. Finally, we validated our findings in independent MI cohorts, using both bulk and single-cell transcriptomic data. Overall, our integrative analysis highlighted both common and specific biological responses to MI across a range of metabolically active tissues.

Competing Interest Statement

JW, MC, DE are employees at AstraZeneca. The other authors declare no conflict of interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 28, 2020.
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Revealing tissue-specific metabolic crosstalk after a myocardial infarction
Muhammad Arif, Martina Klevstig, Rui Benfeitas, Stephen Doran, Hasan Turkez, Mathias Uhlén, Maryam Clausen, Johannes Wikström, Damla Etal, Cheng Zhang, Malin Levin, Adil Mardinoglu, Jan Boren
bioRxiv 2020.10.28.358556; doi: https://doi.org/10.1101/2020.10.28.358556
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Revealing tissue-specific metabolic crosstalk after a myocardial infarction
Muhammad Arif, Martina Klevstig, Rui Benfeitas, Stephen Doran, Hasan Turkez, Mathias Uhlén, Maryam Clausen, Johannes Wikström, Damla Etal, Cheng Zhang, Malin Levin, Adil Mardinoglu, Jan Boren
bioRxiv 2020.10.28.358556; doi: https://doi.org/10.1101/2020.10.28.358556

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