State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):882-890. doi: 10.1016/j.bbadis.2017.12.033. Epub 2017 Dec 26.
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 of Salvia miltiorrhiza Bge., 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.
核因子红细胞 2 相关因子 2（Nrf2）已被证明在动脉粥样硬化中具有保护作用。巨噬细胞中 Nrf2 的缺失会增强泡沫细胞的形成，并促进早期动脉粥样硬化的发生。丹酚酸 C（Tan C）是从丹参的根部分离出来的，丹参是一种传统中药，多年来一直用于治疗多种心血管疾病。本研究旨在测试 Tan C 对巨噬细胞泡沫细胞形成的潜在作用，并探讨其潜在机制。首先，我们观察到 Tan C 显著抑制氧化型低密度脂蛋白（oxLDL）诱导的巨噬细胞泡沫细胞形成。然后，我们发现 Tan C 是巨噬细胞中 Nrf2 和 Sirtuin 1（Sirt1）的激活剂。Tan C 处理后，Nrf2 和 Sirt1 协同激活抗氧化剂过氧化物酶 1（Prdx1）的转录。更重要的是，我们证明沉默 Prdx1 促进 oxLDL 诱导的巨噬细胞泡沫细胞形成。Prdx1 上调三磷酸腺苷结合盒（ABC）转运体 A1（ABCA1）的表达并减少细胞内脂质积累。此外，Tan C 通过依赖于 Prdx1 的方式改善 oxLDL 诱导的巨噬细胞泡沫细胞形成。这些观察结果表明，Tan C 通过激活 Prdx1/ABCA1 信号通路来保护巨噬细胞免受 oxLDL 诱导的泡沫细胞形成，并且 Prdx1 可能是动脉粥样硬化治疗干预的新靶点。
