Investigation of novel LPS-induced differentially expressed long non-coding RNAs in endothelial cells.

The molecular mechanisms responsible for sepsis-induced endothelial dysfunction leading to an elevated risk of cardiovascular diseases remain undefined. Endotoxic or septic shock is a potentially lethal complication of systemic infection by Gram-negative bacteria. Lipopolysaccharide (LPS) is a critical glycolipid component of the outer wall of Gram-negative bacteria, and many of the sepsis-associated cellular signals by Gram-negative bacteria are attributed to LPS. Given that LPS has an established role in the pathophysiology of sepsis and long non-coding RNAs (lncRNAs) have been reported to critically regulate vascular homeostasis, a systematic transcriptional survey was conducted to evaluate the impact of LPS stimulation on human endothelial lncRNAs and protein-coding transcripts (mRNAs). LncRNAs and mRNAs from LPS-treated (100 ng/mL; 24 h) human umbilical vein endothelial cells (HUVECs) were profiled with the Arraystar Human lncRNA Expression Microarray V3.0. Of the 30,584 lncRNAs screened, 871 were significantly upregulated and 1068 significantly downregulated (p < 0.05) in response to LPS. In the same HUVEC samples, 733 of the 26,106 mRNAs screened were upregulated and 536 were downregulated. Among the differentially expressed lncRNAs, AL132709.5 was the most upregulated (~70 fold) and CTC-459I6.1 the most downregulated (~28 fold). Bioinformatics analyses indicated that the differentially expressed upregulated mRNAs are primarily enriched in cytokine-cytokine receptor interaction, infectious diseases, TNF signaling pathway, FoxO signaling pathway, and pathways in cancer. This is the first lncRNA and mRNA transcriptome profile of LPS-mediated changes in human endothelial cells. These observations may reveal novel endothelial targets of LPS that may be involved in the vascular pathology of sepsis.