Low shear stress induces M1 macrophage polarization in murine thin-cap atherosclerotic plaques
Low shear stress induces M1 macrophage polarization in murine thin-cap atherosclerotic plaques
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DOI：
10.1016/j.yjmcc.2015.10.034
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发表时间：
2015-12-01
影响因子：
5
通讯作者：
Monaco, Claudia
中科院分区：
文献类型：
--
作者：
Seneviratne, Anusha N.;Cole, Jennifer E.;Monaco, Claudia
巨噬细胞是动脉粥样硬化斑块的重要组成部分，易发生急性并发症，可以是促炎细胞(M1)、调节性细胞(M2)、脂质细胞(Mox)或血红素诱导的细胞(MHEM)。我们先前的研究表明，在载脂蛋白E基因敲除(ApoE(-/-))小鼠中，低剪应力(LSS)和振荡剪应力(OSS)分别导致薄帽纤维动脉粥样硬化和稳定的富含平滑肌细胞的斑块形成。在这里，我们通过对高脂喂养的载脂蛋白E(-/-)小鼠颈动脉施加剪应力改变管型，研究不同剪应力条件是否与巨噬细胞极化和斑块形态的特定变化有关。铸型后6周，M1标记iNOS和IRF5在LSS病变的巨噬细胞丰富区较OSS病变高表达，而M2标记Arg-1、Mox/MHEM标记HO-1和CD163在OSS病变中升高。我们的数据表明，剪切力可能是动脉粥样硬化中巨噬细胞极化的重要决定因素，低剪切率促进了M1编程。(C)2015爱思唯尔有限公司。保留所有权利。
Macrophages, a significant component of atherosclerotic plaques vulnerable to acute complications, can be pro-inflammatory (designated M1), regulatory (M2), lipid- (Mox) or Heme-induced (Mhem). We showed previously that low (LSS) and oscillatory (OSS) shear stress cause thin-cap fibroatheroma and stable smooth muscle cell-rich plaque formation respectively in ApoE-knockout (ApoE(-/-)) mice. Here we investigated whether different shear stress conditions relate to specific changes in macrophage polarization and plaque morphology by applying a shear stress-altering cast to the carotid arteries of high fat-fed ApoE(-/-) mice. The M1 markers iNOS and IRF5 were highly expressed in macrophage-rich areas of LSS lesions compared to OSS lesions 6 weeks after cast placement, while the M2 marker Arginase-1, and Mox/Mhem markers HO-1 and CD163 were elevated in OSS lesions. Our data indicates shear stress could be an important determinant of macrophage polarization in atherosclerosis, with low shear promoting M1 programming. (C) 2015 Elsevier Ltd. All rights reserved.