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 6weeks 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.

中文翻译：

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低剪切应力在小鼠薄帽动脉粥样硬化斑块中诱导M1巨噬细胞极化。

巨噬细胞是易患急性并发症的动脉粥样硬化斑块的重要组成部分，可以是促炎性的（指定为M1），调节性的（M2），脂质（Mox）或血红素诱导的（Mhem）。我们以前显示过，低（LSS）和振荡（OSS）切应力分别导致ApoE基因敲除（ApoE（-/-））小鼠中的薄帽纤维动脉粥样硬化和稳定的平滑肌细胞丰富斑块形成。在这里，我们通过对高脂喂养的ApoE（-/-）小鼠的颈动脉施加改变切变应力的模型，研究了不同的切应力条件是否与巨噬细胞极化和噬菌斑形态的特定变化有关。与放置石膏后6周的OSS病变相比，M1标记iNOS和IRF5在LSS病变的巨噬细胞富集区域高表达，而M2标记Arginase-1，Mos / Mhem标记HO-1和CD163在OSS病变中升高。我们的数据表明，剪​​切应力可能是动脉粥样硬化中巨噬细胞极化的重要决定因素，低剪切促进了M1程序设计。