Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumaicho Showa, Nagoya, Aichi, 466-8550, Japan.
Sci Rep. 2024 Jul 10;14(1):15878. doi: 10.1038/s41598-024-66791-7.
Apoptosis inhibitor of macrophage (AIM) is known to induce apoptosis resistance in macrophages and to exacerbate chronic inflammation, leading to arteriosclerosis. The role of AIM in aortic aneurysm (AA) remains unknown. This study examined the effects of an anti-AIM antibody in preventing AA formation and progression. In apolipoprotein E-deficient mice, AA was induced by subcutaneous angiotensin II infusion. Mice were randomly divided into two groups: (i) AIM group; weekly anti-murine AIM monoclonal antibody injection (n = 10), and (ii) IgG group; anti-murine IgG antibody injection as control (n = 14). The AIM group, compared with the IgG group, exhibited reduced AA enlargement (aortic diameter at 4 weeks: 2.1 vs. 2.7 mm, respectively, p = 0.012); decreased loss of elastic lamellae construction; reduced expression levels of IL-6, TNF-α, and MCP-1; decreased numbers of AIM-positive cells and inflammatory M1 macrophages (AIM: 1.4 vs. 8.0%, respectively, p = 0.004; M1 macrophages: 24.5 vs. 55.7%, respectively, p = 0.017); and higher expression of caspase-3 in the aortic wall (22.8 vs. 10.5%, respectively, p = 0.019). Our results suggest that administration of an anti-AIM antibody mitigated AA progression by alleviating inflammation and promoting M1 macrophage apoptosis.
巨噬细胞凋亡抑制因子(AIM)已知可诱导巨噬细胞凋亡抵抗,并加重慢性炎症,导致动脉硬化。AIM 在主动脉瘤(AA)中的作用尚不清楚。本研究探讨了抗-AIM 抗体在预防 AA 形成和进展中的作用。在载脂蛋白 E 缺陷小鼠中,通过皮下给予血管紧张素 II 输注来诱导 AA。将小鼠随机分为两组:(i)AIM 组;每周给予抗鼠 AIM 单克隆抗体注射(n=10),和(ii)IgG 组;给予抗鼠 IgG 抗体作为对照(n=14)。与 IgG 组相比,AIM 组 AA 增大减少(4 周时主动脉直径:分别为 2.1 和 2.7mm,p=0.012);弹性板层结构丧失减少;IL-6、TNF-α 和 MCP-1 的表达水平降低;AIM 阳性细胞和炎症性 M1 巨噬细胞数量减少(AIM:分别为 1.4%和 8.0%,p=0.004;M1 巨噬细胞:分别为 24.5%和 55.7%,p=0.017);主动脉壁中 caspase-3 的表达增加(分别为 22.8%和 10.5%,p=0.019)。我们的结果表明,给予抗-AIM 抗体通过减轻炎症和促进 M1 巨噬细胞凋亡来减轻 AA 进展。