With the development of percutaneous coronary, anti-platelet drugs, anti-thrombotic drugs and cardiac surgery, myocardial ischemia-reperfusion injury (MIRI) has received more and more attention. Myocardial ischemia-reperfusion injury (MIRI) is the recovery of blood perfusion in myocardial tissue after a long period of ischemia, which can cause more serious and more obvious damage and dysfunction reperfusion, including decreased systolic function, decreased coronary flow and vascular reactive changes. It can be seen that myocardial ischemia-reperfusion injury has become a major obstacle in clinical treatment, and its harm cannot be ignored. Studying its pathogenesis and exploring effective prevention and treatment measures are of great significance for the treatment of myocardial infarction. Our objectives were i) to determine the underlying genes and molecular pathways associated with MIRI via bioinformatic analysis and (ii) to identify drugs targeting the relevant MIRI molecular pathways.
MIRI-associated genes were searched by text mining, and the intersection of the two gene sets was selected for gene ontology analysis via DAVID database. Protein interaction network analysis was performed via STRING. Enriched cluster genes were analyzed by Cytoscape software. Drug-gene interactions were performed by DGIdb.
552 genes associated with MIRI were identified. A gene cluster including CXCL10, POMC, CXCR3, CX3CR1, CCR5, CCL5, ADCY3, CNR1, ANXA1, C5, FPR2, C5AR1, ADCY7, CCL4, AGTR2, FPR3, KNG1, CNR2
, coupled with chemokine signaling pathway was found to be significant. 14 candidate drugs were targeted as possible mediators in the process of MIRI. According to further analysis, ANXA1
would be a regulator in MIRI affecting the process of programmed cell death. ADCY7, ADCY3
were also found underlying mechanisms for cardioprotective function in MIRI.
This study has improved the comprehensive understanding of the pathogenesis and underlying molecular mechanism in MIRI and proved the availability of bioinformatic methods to search the novel possible connections between genes and diseases. These selected candidate genes and pathways could show us new clues to search the therapeutic targets for the treatment of MIRI. What’s more, this study could also provide the ideas for searching the mechanisms of effective traditional Chinese medicines for MIRI. However, further studies including molecular biological experiments are required to confirm the function of these identified genes in MIRI.