Department of Interventional Radiology, Tongji Hospital of Tongji University, Shanghai 200065, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.12016. Epub 2021 Mar 24.
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‑α, interleukin (IL)‑1β, 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 ‑targets, whereas 12 DELs covered 386 ‑targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses of the ‑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.
炎症可导致血管内皮细胞损伤，是动脉粥样硬化（AS）的主要相关因素之一；因此，抑制内皮炎症是预防 AS 的关键步骤。本研究旨在探讨贝壳杉烯内酯-IIIa（Bak-IIIa）作为贝壳杉烯内酯的重要活性成分，对内皮炎症的作用及其作用机制。用 Bak-IIIa 处理脂多糖（LPS）损伤的人脐静脉内皮细胞（HUVEC）。MTT 检测和酶联免疫吸附试验的结果表明，Bak-IIIa 显著缓解了细胞活力抑制，并降低了 LPS 诱导的 TNF-α、白细胞介素（IL）-1β、IL-8 和 IL-6 的水平。此外，长链非编码 RNA（lncRNA）微阵列分析显示，在 LPS 损伤的 HUVEC 中用 Bak-IIIa 处理后有 70 个差异表达的 lncRNA（DEL）。lncRNA 靶标预测结果显示，44 个 DEL 有 52 个靶标，而 12 个 DEL 覆盖 386 个靶标。靶基因的基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，三个 GO 术语与炎症有关。因此，筛选出 17 个涉及这些 GO 术语的靶基因和 6 个相关的 DEL。通过逆转录定量 PCR 验证，在六个候选物中，NR_015451（LINC00294）的 fold change 最高，而过表达 LINC00294 可显著缓解 LPS 诱导的 HUVEC 活力抑制和炎症损伤。综上所述，Bak-IIIa 通过上调 LINC00294 改善了 LPS 诱导的 HUVEC 炎症损伤。因此，Bak-IIIa 具有预防血管炎症的潜力。
