Integrative transcriptomic analysis of tissue-specific metabolic crosstalk after myocardial infarction

eLife

Johannes Wikström¹  Stephen Doran²  Hasan Turkez³  Martina Klevstig⁴  Jan Boren⁴  Malin Levin⁴  Rui Benfeitas⁵  Muhammad Arif⁶  Mathias Uhlén⁶  Cheng Zhang⁶  Adil Mardinoglu⁷  Damla Etal⁸  Maryam Clausen⁸ 

[1] Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden;Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, United Kingdom;Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum, Turkey;Department of Molecular and Clinical Medicine, University of Gothenburg, The Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden;National Bioinformatics Infrastructure Sweden (NBIS), Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden;Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden;Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden;Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, United Kingdom;Translational Genomics, BioPharmaceuticals R&D, Discovery Sciences, AstraZeneca, Gothenburg, Sweden;

关键词: Systems biology;    network analysis;    whole-body modelling;    myocardial infarction;    multi-tissue;    metabolically active tissues;    Mouse;   

DOI  :  10.7554/eLife.66921

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 hr 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 two independent MI cohorts. Overall, our integrative analysis highlighted both common and specific biological responses to MI across a range of metabolically active tissues.

【 授权许可】

CC BY