Despite decades of research, our understanding of the processes controlling late-stage atherosclerotic plaque stability remains poor. A prevailing hypothesis is that reducing inflammation may improve advanced plaque stability, as recently tested in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial, in which post-myocardial infarction subjects were treated with an IL-1β antibody. Here, we performed intervention studies in which smooth muscle cell (SMC) lineage-tracing Apoe-/- mice with advanced atherosclerosis were treated with anti-IL-1β or IgG control antibodies. Surprisingly, we found that IL-1β antibody treatment between 18 and 26 weeks of Western diet feeding induced a marked reduction in SMC and collagen content, but increased macrophage numbers in the fibrous cap. Moreover, although IL-1β antibody treatment had no effect on lesion size, it completely inhibited beneficial outward remodeling. We also found that SMC-specific knockout of Il1r1 (encoding IL-1 receptor type 1) resulted in smaller lesions nearly devoid of SMCs and lacking a fibrous cap, whereas macrophage-selective loss of IL-1R1 had no effect on lesion size or composition. Taken together, these results show that IL-1β has multiple beneficial effects in late-stage murine atherosclerosis, including promotion of outward remodeling and formation and maintenance of an SMC- and collagen-rich fibrous cap.

中文翻译：

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IL-1β在小鼠晚期动脉粥样硬化病变中具有动脉粥样硬化保护作用。

尽管进行了数十年的研究，但我们对控制晚期动脉粥样硬化斑块稳定性的过程的理解仍然很差。一个普遍的假设是，减少炎症可能会改善晚期斑块的稳定性，正如最近在 Canakinumab 抗炎血栓形成结果研究 (CANTOS) 试验中所测试的那样，在该试验中，心肌梗死后受试者接受了 IL-1β 抗体治疗。在这里，我们进行了干预研究，其中平滑肌细胞 (SMC) 谱系追踪 Apoe-/- 患有晚期动脉粥样硬化的小鼠接受抗 IL-1β 或 IgG 对照抗体治疗。令人惊讶的是，我们发现在西方饮食喂养的 18 至 26 周之间，IL-1β 抗体治疗导致 SMC 和胶原蛋白含量显着降低，但纤维帽中的巨噬细胞数量增加。而且，尽管 IL-1β 抗体治疗对病灶大小没有影响，但它完全抑制了有益的外向重塑。我们还发现 SMC 特异性敲除 Il1r1（编码 1 型 IL-1 受体）导致较小的病灶几乎没有 SMC 且缺乏纤维帽，而 IL-1R1 的巨噬细胞选择性缺失对病灶大小或组成没有影响. 总之，这些结果表明 IL-1β 在晚期小鼠动脉粥样硬化中具有多种有益作用，包括促进外向重塑以及富含 SMC 和胶原蛋白的纤维帽的形成和维持。而 IL-1R1 的巨噬细胞选择性损失对病变大小或组成没有影响。总之，这些结果表明 IL-1β 在晚期小鼠动脉粥样硬化中具有多种有益作用，包括促进外向重塑以及富含 SMC 和胶原蛋白的纤维帽的形成和维持。而 IL-1R1 的巨噬细胞选择性损失对病变大小或组成没有影响。总之，这些结果表明 IL-1β 在晚期小鼠动脉粥样硬化中具有多种有益作用，包括促进外向重塑以及富含 SMC 和胶原蛋白的纤维帽的形成和维持。