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

Elife. 2021 May 11;10:e66921. doi: 10.7554/eLife.66921.

Abstract

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.

Keywords: Systems biology; computational biology; medicine; metabolically active tissues; mouse; multi-tissue; myocardial infarction; network analysis; systems biology; whole-body modelling.

Plain language summary

The human body is like a state-of-the-art car, where each part must work together with all the others. When a car breaks down, most of the time the problem is not isolated to only one part, as it is an interconnected system. Diseases in the human body can also have systemic effects, so it is important to study their implications throughout the body. Most studies of heart attacks focus on the direct impact on the heart and the cardiovascular system. Learning more about how heart attacks affect rest of the body may help scientists identify heart attacks early or create improved treatments. Arif and Klevstig et al. show that heart attacks affect the metabolism throughout the body. In the experiments, mice underwent a procedure that mimics either a heart attack or a fake procedure. Then, Arif and Klevstig et al. compared the activity of genes in the heart, muscle, liver and fat tissue of the two groups of mice 6- and 24-hours after the operations. This revealed disruptions in the immune system, metabolism and the production of proteins. The experiments also showed that changes in the activity of four important genes are key to these changes. This suggests that this pattern of changes could be used as a way to identify heart attacks. The experiments show that heart attacks have important effects throughout the body, especially on metabolism. These discoveries may help scientists learn more about the underlying biological processes and develop new treatments that prevent the harmful systemic effects of heart attacks and boost recovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gene Expression Profiling*
  • Genome
  • Heart / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / metabolism
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / physiopathology
  • Oxidation-Reduction
  • Transcriptome*

Associated data

  • GEO/GSE153485
  • GEO/GSE104187
  • GEO/GSE52313

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.