Aims: Atherosclerosis underlies most cardiovascular diseases, among which acute coronary syndrome (ACS) caused by plaque rupture (PR) often leads to death. Immune-related GTPases (IRGM/Irgm1) have been extensively studied in inflammatory diseases, but their role in atherosclerosis is unclear. Determining how IRGM/Irgm1 promotes atherosclerotic plaque vulnerability will provide information for new biomarkers and/or therapeutic targets. Methods and results: We identified ruptured and unruptured plaques by optical coherence tomography, and found that serum IRGM was highly expressed in patients with ST-segment elevation myocardial infarction in PR. We used ApoE-/-Irgm1+/+, ApoE-/-Irgm1+/- mice and chimeric mice to establish a model of advanced atherosclerosis. The results of pathological experiments showed that Irgm1 caused plaque necrosis. The ratio of neutral lipids and cholesterol crystals increases, while the content of collagen fibers decreases, aggravating the destabilization of atherosclerotic plaques. In vitro, we used multiple approaches to confirm that Irgm1 promotes macrophage apoptosis by promoting the production of reactive oxygen species and activating the MAPK signaling pathway. Conclusions: IRGM may be a potential risk factor for PR. Mechanistic studies have shown that IRGM/Irgm1 contributes to the formation and rupture of fragile plaques. This is partly mediated by the induction of macrophage apoptosis via the MAPK signaling pathway. IRGM may offer new strategies for early treatment of ACS.

中文翻译：

---

IRGM / Irgm1通过MAPK信号通路诱导巨噬细胞凋亡，加剧了动脉粥样硬化的进展。

目的：动脉粥样硬化是大多数心血管疾病的基础，其中由斑块破裂（PR）引起的急性冠脉综合征（ACS）通常导致死亡。免疫相关的GTPases（IRGM / Irgm1）已在炎性疾病中进行了广泛的研究，但它们在动脉粥样硬化中的作用尚不清楚。确定IRGM / Irgm1如何促进动脉粥样硬化斑块易损性将为新的生物标记和/或治疗靶标提供信息。方法和结果：我们通过光学相干断层扫描技术鉴定了破裂和未破裂的斑块，并发现PR中ST段抬高型心肌梗死患者血清IRGM高表达。我们使用ApoE-/-Irgm1 + / +，ApoE-/-Irgm1 +/-小鼠和嵌合小鼠建立晚期动脉粥样硬化模型。病理实验结果表明，Irgm1引起斑块坏死。中性脂质和胆固醇晶体的比例增加，而胶原纤维的含量减少，加剧了动脉粥样硬化斑块的不稳定。在体外，我们使用多种方法来证实Irgm1通过促进活性氧的产生并激活MAPK信号通路来促进巨噬细胞凋亡。结论：IRGM可能是PR的潜在危险因素。机理研究表明，IRGM / Irgm1有助于脆性斑块的形成和破裂。这部分地通过经由MAPK信号传导途径诱导巨噬细胞凋亡来介导。IRGM可能为ACS的早期治疗提供新的策略。我们使用多种方法来证实Irgm1通过促进活性氧的产生并激活MAPK信号通路来促进巨噬细胞凋亡。结论：IRGM可能是PR的潜在危险因素。机理研究表明，IRGM / Irgm1有助于脆性斑块的形成和破裂。这部分地通过经由MAPK信号传导途径诱导巨噬细胞凋亡来介导。IRGM可能为ACS的早期治疗提供新的策略。我们使用多种方法来证实Irgm1通过促进活性氧的产生并激活MAPK信号通路来促进巨噬细胞凋亡。结论：IRGM可能是PR的潜在危险因素。机理研究表明，IRGM / Irgm1有助于脆性斑块的形成和破裂。这部分地通过经由MAPK信号传导途径诱导巨噬细胞凋亡来介导。IRGM可能为ACS的早期治疗提供新的策略。这部分地通过经由MAPK信号传导途径诱导巨噬细胞凋亡来介导。IRGM可能为ACS的早期治疗提供新的策略。这部分地通过经由MAPK信号传导途径诱导巨噬细胞凋亡来介导。IRGM可能为ACS的早期治疗提供新的策略。