Bakkenolide-Iiia Ameliorates Lipopolysaccharide-Induced Inflammatory Injury In Human Umbilical Vein Endothelial Cells By Upregulating Linc00294

Inflammation, which causes injury to vascular endothelial cells, is one of the major factors associated with atherosclerosis (AS); therefore, inhibition of endothelial inflammation is a key step toward preventing AS. The present study aimed to investigate the effects of bakkenolide-IIIa (Bak-IIIa), an important active component of bakkenolides, on endothelial inflammation, as well as the mechanisms underlying such effects. Lipopolysaccharide (LPS)-damaged human umbilical vein endothelial cells (HUVECs) were treated with Bak-IIIa. The results of the MTT assay and enzyme-linked immunosorbent assay indicated that Bak-IIIa significantly alleviated survival inhibition, and decreased the levels of LPS-induced TNF-alpha, interleukin (IL)-1 beta, IL-8, and IL-6. Furthermore, long noncoding RNA (lncRNA) microarray analyses revealed 70 differentially expressed lncRNAs (DELs) in LPS-damaged HUVECs treated with Bak-IIIa. lncRNA target prediction results revealed that 44 DELs had 52 cis-targets, whereas 12 DELs covered 386 trans-targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses of the trans-targets indicated that three GO terms were associated with inflammation. Therefore, 17 targets involved in these GO terms and six relevant DELs were screened out. Validation via reverse transcription-quantitative PCR indicated that the fold change of NR_015451 (LINC00294) was the highest among the six candidates and that overexpression of LINC00294 significantly alleviated LPS-induced survival inhibition and inflammatory damage in HUVECs. In conclusion, Bak-IIIa ameliorated LPS-induced inflammatory damage in HUVECs by upregulating LINC00294. Thus, Bak-IIIa exhibited potential for preventing vascular inflammation.