Ginsenoside Rb2 Alleviated Atherosclerosis by Inhibiting M1 Macrophages Polarization Induced by MicroRNA-216a.
Ginsenoside Rb2 Alleviated Atherosclerosis by Inhibiting M1 Macrophages Polarization Induced by MicroRNA-216a.
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人参皂苷 Rb2 通过抑制 MicroRNA-216a 诱导的 M1 巨噬细胞极化减轻动脉粥样硬化
DOI：
10.3389/fphar.2021.764130
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发表时间：
2021
影响因子：
5.6
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Wang S;Yang S;Chen Y;Chen Y;Li R;Han S;Kamili A;Wu Y;Zhang W
简介：动脉粥样硬化是一种慢性疾病，其特征是炎症过程和脂质沉积。我们之前报道了microRNA-216 a（miR-216 a）可以通过促进M1促炎表型的极化来加速动脉粥样硬化的进展。人参皂苷Rb 2（Ginsenoside Rb 2，Rb 2）是从人参中提取的主要抗肿瘤活性物质，与miR-216 a具有高亲和力。在这项研究中，我们的目的是研究Rb 2是否可以抵消巨噬细胞中miR-216 a的作用，以改善动脉粥样硬化。 研究方法：通过尾静脉慢性感染载脂蛋白E缺乏（ApoE−/−）小鼠模型的miR-216 a腺病毒，然后腹腔内注射Rb 2。检测胸主动脉斑块病变面积及稳定性。体外培养人髓系白血病单核细胞（THP-1）或人外周血单核细胞（PBMC），转染miR-216 a模拟物，并给予Rb 2处理，探讨Rb 2对M1巨噬细胞极化、炎症过程和脂质积聚的作用机制。 结果如下：在动脉粥样硬化ApoE−/−小鼠模型中，miR-216 a极大地增加了胸主动脉的正面主动脉病变面积、脂质蓄积和斑块中的M1巨噬细胞浸润，而Rb 2处理显著减轻了miR-216 a对动脉粥样硬化负荷的这些影响。在体外THP-1模型中，流式细胞术实验显示Rb 2处理抑制了由表面标记物CD 86表达表征的M1巨噬细胞的miR-216 a介导的极化，但对由表面标记物CD 206表达表征的M2极化没有影响。机制上，Rb 2通过Smad 3/核因子κ B抑制剂α途径抑制miR-216 a介导的炎症反应。此外，Rb 2通过抵消miR-216 a在氧化低密度脂蛋白下的THP-1来源的泡沫细胞和PBMC来源的泡沫细胞中的作用来减少脂质摄取并促进胆固醇流出。 结论：我们的研究结果表明，Rb 2可能是一个潜在的治疗动脉粥样硬化的分子，通过减少动脉粥样硬化斑块病变，脂质积累，和M1巨噬细胞极化通过靶向miR-216 a。考虑到内膜中泡沫细胞的积累是长期发生的，Rb 2在动脉粥样硬化进展中的作用需要进一步研究。
Introduction: Atherosclerosis is a chronic disease characterized by the inflammatory process and lipid depositions. We previously reported that microRNA-216a (miR-216a) can accelerate the progression of atherosclerosis by promoting the polarization of M1 pro-inflammatory phenotype. Ginsenoside Rb2 (Rb2), the major pharmacologically active compound extracted from ginseng, has a high affinity to miR-216a. In this study, we aimed to investigate whether Rb2 can counteract the effect of miR-216a in macrophages to ameliorate atherosclerosis. Methods: The apolipoprotein E deficiency (ApoE−/−) mice model was chronically infected with miR-216a adenovirus via the tail vein and then intraperitoneally injected with Rb2. The plaque lesion area and stability of thoracic aorta were examined. The human myeloid leukemia mononuclear cells (THP-1) or human peripheral blood mononuclear cells (PBMCs) were cultured in vitro, transfected with miR-216a mimics, and treated with Rb2 to explore the mechanisms of Rb2 on the polarization of M1 macrophages, inflammatory process, and lipid accumulation. Results: In the atherosclerotic ApoE−/− mice model, miR-216a greatly increased en face aortic lesion area of the thoracic aorta, lipid accumulation, and M1 macrophages infiltration in plaques, whereas these effects of miR-216a on atherosclerosis burden were significantly alleviated by Rb2 treatment. In the in vitro THP-1 model, the flow cytometry experiment showed that Rb2 treatment inhibited miR-216a–mediated polarization of M1 macrophages characterized by the surface marker CD86 expression but had no effects on M2 polarization characterized by the surface marker CD206 expression. Mechanistically, Rb2 suppressed the miR-216a–mediated inflammatory response through the Smad3/nuclear factor kappa B inhibitor alpha pathway. Moreover, Rb2 reduced the lipid uptake and promoted cholesterol efflux by counteracting the effects of miR-216a in the THP-1–derived foam cells and in the PBMC-derived foam cells under the oxidized low-density lipoproteins. Conclusion: Our findings indicated that Rb2 might be a potential therapeutic molecule for atherosclerosis by attenuating the atherosclerosis plaque lesion, lipid accumulation, and M1 macrophages polarization by targeting miR-216a. Given that accumulation of foam cells in the intima takes place chronically, the role of Rb2 in atherosclerosis progression needs further investigation.
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影响因子：
8.1
作者：
Serbulea V;Upchurch CM;Ahern KW;Bories G;Voigt P;DeWeese DE;Meher AK;Harris TE;Leitinger N
通讯作者：
Leitinger N
影响因子：
5
作者：
Qi JR;Zhao DR;Zhao L;Luo F;Yang M
通讯作者：
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影响因子：
20.1
作者：
Tabas I;Bornfeldt KE
通讯作者：
Bornfeldt KE
人参皂苷 Rb2 对 microRNA 介导的内皮衰老和炎症的抑制作用-216a
影响因子：
3.4
作者：
Chen, Yutong;Wang, Shuting;Zhang, Weili
通讯作者：
Zhang, Weili
MicroRNA-216a 通过 Smad3/I kappa B α 通路诱导内皮衰老和炎症
影响因子：
5.3
作者：
Yang S;Mi X;Chen Y;Feng C;Hou Z;Hui R;Zhang W
通讯作者：
Zhang W