Background. Numerous studies have highlighted that long noncoding RNA (lncRNA) can indirectly regulate the expression of mRNAs by binding to microRNA (miRNA). LncRNA-associated ceRNA networks play a vital role in the initiation and progression of several pathological mechanisms. However, the lncRNA-miRNA-mRNA ceRNA network in endothelial cells under cyclic stretch is seldom studied. Methods. The miRNA, mRNA, and lncRNA expression profiles of 6 human umbilical vein endothelial cells (HUVECs) under circumferential stress were obtained by next-generation sequencing (NGS). We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the R software package GDCRNATools. Cytoscape was adopted to construct a lncRNA-miRNA-mRNA ceRNA network. In addition, through GO and KEGG pathway annotations, we analyzed gene functions and their related pathways. We also adopted ELISA and TUNEL to investigate the effect of si-NEAT1 on endothelial inflammation and apoptosis. Results. We recognized a total of 32978 lncRNAs, 1046 miRNAs, and 31958 mRNAs in 6 samples; among them, 155 different expressed lncRNAs, 74 different expressed miRNAs, and 960 different mRNAs were adopted. Based on the established theory, the ceRNA network was composed of 13 lncRNAs, 44 miRNAs, and 115 mRNAs. We constructed and visualized a lncRNA-miRNA-mRNA network, and the top 20 nodes are identified after calculating their degrees. The nodes with most degrees in three kinds of RNAs are hsa-miR-4739, NEAT1, and MAP3K2. Functional analysis showed that different biological processes enriched in biological regulation, response to stimulus and cell communication. Pathway analysis was mainly enriched in longevity regulating, cell cycle, mTOR, and FoxO signaling pathway. Circumferential stress can significantly downregulate NEAT1, and after transducing si-NEAT1 for 24 h, inflammatory cytokine IL-6 and MCP-1 were significantly increased; furthermore, fewer TUNEL-positive cells were found in the si-NEAT1 treated group. Conclusions. The establishing of a ceRNA network can help further understand the mechanism of vein graft failure. Our data demonstrated that NEAT1 may be a core factor among the mechanical stress factors and that cyclic stress can significantly reduce expression of NEAT1, give rise to inflammation in the early stage of endothelial dysfunction, and promote EC apoptosis, which may play an essential role in vein graft failure.

Background. The purpose of this cohort study was to investigate the independent relationship between preoperative statin therapy (PST) and postoperative severe multiorgan failure, measured by the Sequential Organ Failure Assessment (SOFA) maximum greater than 11, in high-risk patients undergoing isolated coronary artery bypass grafting (CABG). Methods. The present study is a perspective, single-center, cohort analysis enrolling high-risk patients undergoing CABG from Jan 1, 2018, to Dec 31, 2018, in Beijing Anzhen hospital. Results. Among a total of 880 high-risk patients undergoing isolated CABG included in this study, 503 (57.2%) experienced statin therapy before CABG. The SOFA maximum was significantly lower in the PST group compared with the control group (7.8 ± 3.0 v 9.2 ± 3.4, P<0.0001). Multivariate logistic regression analysis demonstrated the incidence of the severe multiorgan dysfunction, measured by SOFA maximum ≥11, was dramatically reduced in the PST group (OR, 0.68, 95% CI 0.50–0.92, P=0.013). Furthermore, preoperative statin therapy (PST) might be associated with a decreased risk of postoperative major adverse cardiovascular and cerebral events and acute kidney injury, but an increased risk of postoperative hepatic inadequacy. Conclusion. SOFA maximum was significantly lower in the PST group compared with the control group and the incidence of the severe multiorgan dysfunction was dramatically reduced in the PST group. The findings of this study might shed new light on questions of positive or negative effects of PST on multiple organ function after high-risk CABG, so as to ultimately improve high-risk patient in-hospital outcomes from CABG.

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