AUTHOR=Badawi Sally , Paccalet Alexandre , Harhous Zeina , Pillot Bruno , Augeul Lionel , Van Coppenolle Fabien , Lachuer Joel , Kurdi Mazen , Crola Da Silva Claire , Ovize Michel , Bidaux Gabriel 

TITLE=A Dynamic Transcriptional Analysis Reveals IL-6 Axis as a Prominent Mediator of Surgical Acute Response in Non-ischemic Mouse Heart

JOURNAL=Frontiers in Physiology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2019.01370

DOI=10.3389/fphys.2019.01370

ISSN=1664-042X

ABSTRACT=Background: 
Ischemic heart diseases are a major cause of death worldwide. Different animal models, including cardiac surgery, have been developed over time. Unfortunately, the surgery models have been reported to trigger an important inflammatory response that might be an effect modifier, where involved molecular processes have not been fully elucidated yet.
Objective:
We sought to perform a thorough characterization of the sham effect in the myocardium and identify the interfering inflammatory reaction in order to avoid misinterpretation of the data via systems biology approaches. 
Methods and Results:
We combined a comprehensive analytical pipeline of mRNAseq dataset and systems biology analysis to characterize the acute phase response of mouse myocardium at 0, 45 minutes and 24 hours after surgery to better characterize the molecular processes inadvertently induced in sham animals.
Our analysis showed that the surgical intervention induced 1209 differentially expressed transcripts (DETs). The clustering of positively co-regulated transcript modules at 45min fingerprinted the activation of signalization pathways, while positively co-regulated genes at 24 hrs identified the recruitment of neutrophils and the differentiation of macrophages. In addition, we combined the prediction of transcription factors (TF) regulating DETs with protein-protein interaction networks built from these TFs to predict the molecular network which have induced the DETs. By mean of this retro-analysis of processes upstream gene transcription, we revealed a major role of the Il-6 pathway and further confirmed a significant increase in circulating IL-6 at 45min after surgery. 
Conclusion:
This study suggests that a strong induction of the IL-6 axis occurs in sham animals over the first 24hrs and leads to the induction of inflammation and tissues’ homeostasis processes.