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.
Highlights
Cardiovascular disease (CVD) is the leading cause of death worldwide, accounting for more than 17 million deaths globally in 2016 1
To study global biological alterations and systemic whole-body effects associated with Myocardial infarction (MI), we obtained heart, liver, skeletal muscle, and white adipose tissue from mice 6 h and 24 h after either an MI or a sham operation
We generated transcriptomics data and identified differentially expressed genes (DEGs) 6 and 24 h post MI and sham operation in all tissues, with the most significant differences occurring after 24 h (Supplementary File 1, Figure 1B)
Summary
Cardiovascular disease (CVD) is the leading cause of death worldwide, accounting for more than 17 million deaths globally in 2016 1. Many behavioral risk factors (including unhealthy diet, physical inactivity, excessive use of alcohol, and tobacco consumption), which are responsible for hypertension, obesity, diabetes, and hyperlipidemia by significantly altering metabolism, are implicated in MI. These abnormalities are known as the high-risk factors of MI and CVDs in general. The use of systems biology has aided the discovery of new therapeutic approaches in multiple diseases 2-4 by identifying novel therapeutic agents and repositioning of existing drugs 5. Multiple studies in individual tissues have been performed and provided new insights into the underlying mechanisms of diseases 12-15. We used several systems biology approaches to obtain a systematic picture of the metabolic alterations that occur after an MI (Figure 1A), and validated our findings in two independent datasets
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