Scientists have mapped out the alterations in metabolism that occur following a heart attack, and the results of their study were published recently in the open-access journal eLife.
Heart Attack. Image Credit: lovelyday12/Shutterstock.com
Their research in mice uncovered specific genes and metabolic pathways that could hinder or support recovery and may be ideal candidates for treatments to avoid damage following a heart attack.
Although some studies have looked at how changes in individual body tissues underlie mechanisms of disease, the crosstalk between different tissues and their dysregulation has not been examined in heart attacks or other cardiovascular-related complications.”
Muhammad Arif, Study First Author and PhD Student, KTH Royal Institute of Technology, Stockholm, Sweden
“In this study, we performed an integrated analysis of heart and other metabolically active tissues using a mouse model of heart attack and used systems biology approaches to get a systematic picture of the metabolic changes that occur,” added Arif.
Systems biology has assisted in the development of novel therapeutic methods for a variety of diseases. Instead of taking systems apart and analyzing their components, the process involves taking measurements from various tissues and cells and using them to reproduce the system under study.
The team used a systems biology technique known as co-expression networks (CNs) in this study to demonstrate how the roles of genes in various tissues are related together.
First, they measured the function of all the genes of four tissue types in mice that had a heart attack: fat, liver skeletal muscle, and heart. They compared this to gene activity in mice that had not had a heart attack to produce sets of differentially expressed genes (DEGs) that were specific to each tissue.
Then, in the co-expression network study, they looked at the top 5% of genes that were the most closely related across the four tissues. They then used the DEG findings to look at how the top 5% of genes changed 24 hours after a heart attack.
They discovered essential clusters of genes that were altered in various tissues after a heart attack. Gene variations in the muscle and heart tended to be associated with energy production and muscle contraction. The gene modifications in the liver were linked to fat transport and metabolism, as well as the metabolism of cell-protecting substances like glutathione.
The researchers then used this data to create a multi-tissue model of the metabolic response to a heart attack and compared their findings to previous research on heart tissue. Four genes were shown to be consistently altered in all experiments.
These genes are believed to be involved in muscle contraction, energy production, and protein production, and at least one of them is being investigated as a potential drug target for cardiovascular disease.
Taken together, the findings show that after a heart attack, there is a decrease in heart-specific functions and an increase in fat metabolism and inflammation in the muscle, heart, and fat tissue. The team observed a distinct reaction in the liver, where inflammation was decreased.
Our integrative analysis highlights both common and tissue-specific biological responses to a heart attack across a range of metabolically active tissues. The approach demonstrates a way of using multi-tissue gene activity data to identify changes in biological processes and pathways and systematically explore the effects of a disease.”
Adil Mardinoglu, Study Senior Author and Professor, Systems Biology, KTH Royal Institute of Technology, Sweden, King’s College London, UK
“This opens up new opportunities for future research into the pathways identified, and the potential to use a similar approach to understand other complex human diseases,” concluded Mardinoglu.
Arif, M., et al. (2021) Integrative transcriptomic analysis of tissue-specific metabolic crosstalk after myocardial infarction. eLife. doi.org/10.7554/eLife.66921.