Tanshindiol C inhibits oxidized low-density lipoprotein induced macrophage foam cell formation via a peroxiredoxin 1 dependent pathway
Tanshindiol C inhibits oxidized low-density lipoprotein induced macrophage foam cell formation via a peroxiredoxin 1 dependent pathway
复制标题
丹参二醇 C 通过过氧化还原蛋白 1 依赖性途径抑制氧化低密度脂蛋白诱导的巨噬细胞泡沫细胞形成
DOI：
10.1016/j.bbadis.2017.12.033
复制
发表时间：
2018
影响因子：
6.2
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Yang Yuyu;Li Xueyan;Peng Liying;An Lin;Sun Ningyuan;Hu Xuewen;Zhou Ping;Li Ping;Chen Jun;Xu Yong;Li P;Chen J
NF-E2相关因子2（Nrf 2）已被证明在动脉粥样硬化中具有保护作用。巨噬细胞中Nrf 2的缺失增强泡沫细胞形成并促进早期动脉粥样硬化形成。丹参二醇C（Tanshindiol C，Tan C）是从丹参（Salvia millionrhizaBge.）多年来一直用于治疗多种心血管疾病的传统中药。本研究旨在检测TanC对巨噬细胞泡沫细胞形成的潜在作用并探讨其机制。首先，我们观察到谭C显着抑制氧化低密度脂蛋白（oxLDL）诱导的巨噬细胞泡沫细胞的形成。然后，我们发现Tan C是巨噬细胞中Nrf 2和Sirtuin 1（Sirt 1）的激活剂。在Tan C处理后，Nrf 2和Sirt 1协同激活抗氧化剂过氧化物酶1（Prdx 1）的转录。更重要的是，我们证明Prdx 1的沉默促进oxLDL诱导的巨噬细胞泡沫细胞形成。Prdx 1上调三磷酸腺苷结合盒（ABC）转运蛋白A1（ABCA 1）的表达，并减少细胞内脂质的积累。此外，谭C改善oxLDL诱导的巨噬细胞泡沫细胞形成的Prdx 1依赖性的方式。这些观察结果表明，谭C保护巨噬细胞oxLDL诱导的泡沫细胞形成通过激活Prdx 1/ABCA 1信号和Prdx 1可能是一个新的目标动脉粥样硬化的治疗干预。
NF-E2-related factor 2 (Nrf2) has been shown to be protective in atherosclerosis. The loss of Nrf2 in macrophages enhances foam cell formation and promotes early atherogenesis. Tanshindiol C (Tan C) is isolated from the root ofSalvia miltiorrhizaBge., a traditional Chinese medicine that has been used for the treatment of several cardiovascular diseases for many years. This study was aimed to test the potential role of Tan C against macrophage foam cell formation and to explore the underlying mechanism. Firstly, we observed that Tan C markedly suppressed oxidized low-density lipoprotein (oxLDL) induced macrophage foam cell formation. Then, we found that Tan C was an activator of both Nrf2 and Sirtuin 1 (Sirt1) in macrophages. Nrf2 and Sirt1 synergistically activated the transcription of anti-oxidant peroxiredoxin 1 (Prdx1) after Tan C treatment. More important, we demonstrated that silencing of Prdx1 promoted oxLDL-induced macrophage foam cell formation. Prdx1 upregulated adenosine triphosphate-binding cassette (ABC) transporter A1 (ABCA1) expression and decreased intracellular lipid accumulation. Furthermore, Tan C ameliorated oxLDL induced macrophage foam cell formation in a Prdx1-dependent manner. These observations suggest that Tan C protects macrophages from oxLDL induced foam cell formation via activation of Prdx1/ABCA1 signaling and that Prdx1 may be a novel target for therapeutic intervention of atherosclerosis.