Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
Food Funct. 2020 Feb 26;11(2):1881-1890. doi: 10.1039/c9fo01976f.
β-Sitosterol is a natural compound widely found in many vegetable oils, nuts, and plant medicines; it lowers the cholesterol levels, enhances the production of plasminogen activators, and exhibits anticancer and antiatherogenic effects. However, the direct endothelial protection of β-sitosterol against an oxidized low-density lipoprotein (ox-LDL) is not well understood. In the present study, β-sitosterol significantly inhibited cell apoptosis (P < 0.01), increased cell migration (P < 0.01), improved energy metabolism (P < 0.05) and improved morphology after ox-LDL (50 μg ml-1) exposure following β-sitosterol (2 μg mL-1) treatment in human aortic endothelial cells (HAECs ). A total of 691 differentially expressed (DE) mRNAs were identified (579 were upregulated and 112 were downregulated, fold change ≥2.0, P < 0.05) after 24 h of β-sitosterol administration in transcriptome sequencing (β-sitosterol vs. ox-LDL), which suggested that β-sitosterol reversed 62.32% change in mRNAs induced by ox-LDL. DE mRNAs are enriched mainly in focal adhesion, ribosomes, eukaryotic translation elongation, etc. Considering that one of the enrichment is 3'-UTR-mediated translational regulation, we explored DE microRNA (miRNA). The miRNA-seq data proposed 87 up-regulated and 58 down-regulated miRNAs (fold change ≥2.0, P < 0.05) in miRNA-seq (β-sitosterol vs. ox-LDL), suggesting that β-sitosterol reversed 76.67% change in miRNAs induced by ox-LDL. The DE miRNA-DE mRNA coexpression network focused on ribosomes, cell cycle, oxidative phosphorylation, PI3K-Akt signaling pathway, TNF signaling pathway, ErbB signaling pathway, and mTOR signaling pathway. Consequently, miRNAs might be the targets of β-sitosterol and play vital roles in transcriptional regulation in endothelial protective and antiatherogenic effects against ox-LDL.
β-谷甾醇是一种广泛存在于多种植物油、坚果和植物药中的天然化合物；它能降低胆固醇水平，增强纤溶酶原激活物的产生，并具有抗癌和抗动脉粥样硬化作用。然而，β-谷甾醇对氧化型低密度脂蛋白（ox-LDL）的直接内皮保护作用尚不清楚。在本研究中，β-谷甾醇显著抑制细胞凋亡（P<0.01），增加细胞迁移（P<0.01），改善能量代谢（P<0.05），改善 ox-LDL（50μgml-1）暴露后细胞形态（P<0.05），经β-谷甾醇（2μgmL-1）处理后，人主动脉内皮细胞（HAECs）。在转录组测序（β-谷甾醇 vs. ox-LDL）中，β-谷甾醇给药 24 小时后，共鉴定出 691 个差异表达（DE）mRNA（579 个上调，112 个下调，倍数变化≥2.0，P<0.05），这表明β-谷甾醇逆转了 ox-LDL 诱导的 62.32%的 mRNA 变化。DE mRNAs 主要富集在粘着斑、核糖体、真核翻译延伸等。考虑到富集之一是 3'-UTR 介导的翻译调控，我们探索了 DE 微小 RNA（miRNA）。miRNA-seq 数据提出了 87 个上调和 58 个下调的 miRNA（倍数变化≥2.0，P<0.05），在 miRNA-seq（β-谷甾醇 vs. ox-LDL）中，这表明β-谷甾醇逆转了 ox-LDL 诱导的 76.67%的 miRNA 变化。DE miRNA-DE mRNA 共表达网络主要集中在核糖体、细胞周期、氧化磷酸化、PI3K-Akt 信号通路、TNF 信号通路、ErbB 信号通路和 mTOR 信号通路。因此，miRNA 可能是β-谷甾醇的靶点，并在 ox-LDL 诱导的内皮保护和抗动脉粥样硬化作用的转录调控中发挥重要作用。
