Diabetes mellitus is an important risk factor to increase the risk of cardiovascular diseases. According to previous research[12–14],a series of pathophysiological changes caused by acute myocardial infarction in diabetic patients significantly increase the incidence and mortality of heart failure. The cause of this series of pathophysiological changes is still unclear, and studies have shown that different gene expression has a great impact on the prognosis of DM after acute myocardial ischemia[15].LncRNA, a subclass of non-coding RNA, participates in many physiological and pathological regulatory processes of the body, and has been widely studied and applied in oncology. However, the research on myocardial I/R injury have received relatively little attention, and the complex mechanism and signal pathway involved in lncRNA still need to be further clarified. Yang et al [16]confirmed that the expression of lncRNA Kcnq1ot1 was increased in cardiomyocytes induced by high glucose and cardiac tissues of DM mouse. Silencing Kcnq1ot1 moderated pyroptosis, reduced cell death, improved cytoskeleton structure abnormalities and calcium overload in vitro, and improved heart function and morphology in vivo. Another recent finding found that the expression of a novel lncRNA, myocardial infarction associated transcript 1(Mirt1) was upregulated in acute myocardial infarction. Knockdown of Mirt1 improved cardiac functions, decreased cardiomyocytes apoptosis, attenuated inflammatory cell infiltration in vivo, and inhibited NF-κB signaling pathway in vitro[17].
In the present study, we found 2,476 lncRNAs and 710 mRNAs using high-throughput sequencing analysis. The differentially expressed lncRNAs were selected as described previously,TCONS_00036439,TCONS_00151548,TCONS_00153276,TCONS_00344188,TCONS_00277692,TCONS_00236469,TCONS_00236468 were markedly upregulated. Conversely, TCONS_00153290,TCONS_00360941,TCONS_00142622 were downregulated. To predict the potential roles of the differentially expressed lncRNAs,we performed GO and pathway analysis to identify the biological functions and mechanisms of the coding genes associated with the significantly differentially expressed lncRNAs. It revealed that the dysregulated transcripts were most highly enriched in inflammatory response, immune response, response to hypoxia, sarcomere, outward rectifier potassium channel activity GO terms. Additionally, we used KEGG pathway analysis and found that these lncRNAs are involved in Cytokine-cytokine receptor interaction, JAK-STAT signaling pathway ,TNF signaling pathway, glucolipid metabolism. Furthermore, a gene co-expression network was constructed to identify correlated targets of highly-regulated lncRNAs. Some of the targets mentioned here have been reported to be related to ischemia-reperfusion injury: as for Sestrin2 has been redefined as an LKB1-AMPK scaffold to initiate AMPK activation in the ischemic heart;AGO1 was targeted by hypoxia-responsive microRNAs to enhance angiogenesis in vitro and in vivo. To further investigate the inter-regulation of lncRNAs and mRNAs involved in IRI, function gain or loss experiments are needed.
However,there are some disadvantages in our study. First, we only predicted lncRNA functions through lncRNA-mRNA co-expression network analysis. Second,high-throughput sequencing technology faces several challenges,including complex library construction and efficient methods to store, retrieve and process large amounts of data. Third,larger sample sizes are required to verify the results in future research.