ObjectiveThis study was designed to show the time-dependent changes in the expression profiles of long non-coding RNAs (lncRNAs) in rat vein grafts by using the high-throughput sequencing technique, and subsequently figure out lncRNAs related to vein graft failure.MethodsThe whole SD rats were randomly classified into four groups according to different sampling time points (0, 7, 14 and 28 days after surgery, respectively;n=3 per group). The day 0 group was set as a control, and the other three groups were set as experimental groups (the model of external jugular vein-carotid artery bypass was prepared in the experimental group). We identified the differentially expressed lncRNAs of the vein graft sample at different sampling time points with high-throughput sequencing, and verified these results using the technique of real-time quantitative PCR (RT-qPCR). Meanwhile, we used Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to screen lncRNAs which may play roles in the restenosis process of vein grafts. The function of lncRNA-mRNA pairs was predicted. We subsequently used RT-qPCR to verify these lncRNAs.ResultsA total of 2 572 sustained differentially expressed lncRNAs were identified in our study. We showed the top ten differentially expressed lncRNAs at each post-operative time point. Through GO analysis and KEGG pathway analysis, we revealed the sustained differentially expressed genes which may be involved in VGF-related biological process, cellular component, molecular function and biological pathways. Finally, we screened 15 pairs of lncRNA-mRNA, includingMRAK083052-Nrp1, which may play roles in mediating the restenosis of vein graft. And the results of RT-qPCR were consistent with the results of the high-throughput sequencing.ConclusionThe present study investigated the time-dependent changes in the expression profiles of lncRNAs in vein grafts. We also screened 15 pairs of lncRNA-mRNA which may paly roles in vein graft failure.