Uncovering Potential lncRNAs and mRNAs in the Progression From Acute Myocardial Infarction to Myocardial Fibrosis to Heart Failure.

Background: Morbidity and mortality of heart failure (HF) post-myocardial infarction (MI) remain elevated. The aim of this study was to find potential long non-coding RNAs (lncRNAs) and mRNAs in the progression from acute myocardial infarction (AMI) to myocardial fibrosis (MF) to HF. Methods: Firstly, blood samples from AMI, MF, and HF patients were used for RNA sequencing. Secondly, differentially expressed lncRNAs and mRNAs were obtained in MF vs. AMI and HF vs. MF, followed by functional analysis of shared differentially expressed mRNAs between two groups. Thirdly, interaction networks of lncRNA-nearby targeted mRNA and lncRNA-co-expressed mRNA were constructed in MF vs. AMI and HF vs. MF. Finally, expression validation and diagnostic capability analysis of selected lncRNAs and mRNAs were performed. Results: Several lncRNA-co-expressed/nearby targeted mRNA pairs including AC005392.3/AC007278.2-IL18R1, AL356356.1/AL137145.2-PFKFB3, and MKNK1-AS1/LINC01127-IL1R2 were identified. Several signaling pathways including TNF and cytokine-cytokine receptor interaction, fructose and mannose metabolism and HIF-1, hematopoietic cell lineage and fluid shear stress, and atherosclerosis and estrogen were selected. IL1R2, IRAK3, LRG1, and PLAC4 had a potential diagnostic value for both AMI and HF. Conclusion: Identified AC005392.3/AC007278.2-IL18R1, AL356356.1/AL137145.2-PFKFB3, and MKNK1-AS1/LINC01127-IL1R2 lncRNA-co-expressed/nearby targeted mRNA pairs may play crucial roles in the development of AMI, MF, and HF.