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Review
. 2022 Apr 26;9(5):132.
doi: 10.3390/jcdd9050132.

Signaling Pathways Involved in Myocardial Ischemia-Reperfusion Injury and Cardioprotection: A Systematic Review of Transcriptomic Studies in Sus scrofa

Hector Salazar-Gonzalez  1 , Yanet Karina Gutierrez-Mercado  2 , Francisco Javier Munguia-Galaviz  3   4 , Raquel Echavarria  5
Affiliations
Review

Signaling Pathways Involved in Myocardial Ischemia-Reperfusion Injury and Cardioprotection: A Systematic Review of Transcriptomic Studies in Sus scrofa

Hector Salazar-Gonzalez et al. J Cardiovasc Dev Dis. .

Abstract

Myocardial damage in acute myocardial infarctions (AMI) is primarily the result of ischemia−reperfusion injury (IRI). Recognizing the timing of transcriptional events and their modulation by cardioprotective strategies is critical to address the pathophysiology of myocardial IRI. Despite the relevance of pigs for translational studies of AMI, only a few have identified how transcriptomic changes shape cellular signaling pathways in response to injury. We systematically reviewed transcriptomic studies of myocardial IRI and cardioprotection in Sus scrofa. Gene expression datasets were analyzed for significantly enriched terms using the Enrichr analysis tool, and statistically significant results (adjusted p-values of <0.05) for Signaling Pathways, Transcription Factors, Molecular Functions, and Biological Processes were compared between eligible studies to describe how these dynamic changes transform the myocardium from an injured and inflamed tissue into a scar. Then, we address how cardioprotective interventions distinctly modulate the myocardial transcriptome and discuss the implications of uncovering gene regulatory networks for cardiovascular pathologies and translational applications.

Keywords: RNA-seq; cardioprotection; microarrays; myocardial ischemia; signaling pathways; swine; transcriptomics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Diagram of the systematic review process.
Figure 2
Figure 2
Active Signaling Pathways (SPs) in the Infarct Core (A) and the Border Zone (B). For each histological area, upregulated genes registered in the published data sets were analyzed separately using Enrichr and g: Profiler to identify active SPs. Only results with significant adjusted p-values (<0.05) were considered as active in the tissues corresponding to each data set. Identified active SPs in at least two data sets were defined as active in this comprehensive IRI analysis. Active SPs were ordered chronologically. Colored boxes indicate the active SPs. Active SPs common to the Infarct Core and the Border Zone are highlighted in grey. Listed Active SPs from each histological area were compared to identify similarities using a Venn diagram (not shown).
Figure 3
Figure 3
Active Transcription Factors (TFs) in the Infarct Core (A) and the Border Zone (B). For each histological area, upregulated genes registered in the published data sets were analyzed separately using Enrichr to identify active TFs in each study. Only results with significant adjusted p-values (<0.05) were considered as active in the tissues corresponding to each data set. Identified active TFs in at least two data sets were defined as active in this comprehensive IRI analysis. Active TFs were ordered chronologically. Colored boxes indicate the active TFs. Active TFs common to the Infarct Core and the Border Zone are highlighted in grey. Listed Active TFs from each histological area were compared to identify similarities using a Venn diagram (not shown).
Figure 4
Figure 4
Active molecular functions and body processes in the Infarct Core (A) and the Border Zone (B). For each histological area, upregulated genes registered in the published data sets were analyzed separately using Enrichr and g: Profiler to identify active MFs and BPs in each study. Only results with significant adjusted p-values (<0.05) were considered as active in the tissues corresponding to each data set. Identified active MFs and BPs in at least two data sets were defined as active in this comprehensive IRI analysis. Functions and Processes were ordered chronologically. Colored boxes indicate the active Functions and Processes.
Figure 5
Figure 5
Cell signaling pathways modulated by IPC. IPC models (A) SWOP; (B) RCO; (C) RCS; (D) Main cardioprotective pathways up and downregulated in all three models of IPC, highlighting their widespread cardioprotective potential in myocardial IRI.
Figure 6
Figure 6
Spatiotemporal pathways transcriptionally modulated after myocardial IRI in swine.
Figure 7
Figure 7
Cardioprotective pathways in myocardial IRI.
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