Background. Ferroptosis is a new form of cell death, which is closely related to the occurrence of many diseases. Our work focused on the mechanism by which HMGB2 regulate ferroptosis and inflammation in abdominal aortic aneurysm (AAA). Methods. Reverse transcription–quantitative polymerase chain reaction and western blot were utilized to assess HMGB2 levels. CCK-8 and flow cytometry assays were utilized to measure cell viability and apoptosis. We detected reactive oxygen species generation, Fe²⁺ level, and ferroptosis-related protein levels in Ang-II-treated VSMCs, which were typical characteristics of ferroptosis. Finally, the mice model of AAA was established to verify the function of HMGB2 in vivo. Results. Increased HMGB2 level was observed in Ang-II-treated VSMCs and Ang-II-induced mice model. HMGB2 depletion accelerated viability and impeded apoptosis in Ang-II-irritatived VSMCs. Moreover, HMGB2 deficiency neutralized the increase of ROS in VSMCs caused by Ang-II. HMGB2 silencing considerably weakened Ang-II-caused VSMC ferroptosis, as revealed by the decrease of Fe²⁺ level and ACSL4 and COX2 levels and the increase in GPX4 and FTH1 levels. Furthermore, the mitigation effects of shHMGB2 on Ang-II-induced VSMC damage could be counteracted by erastin, a ferroptosis agonist. Mechanically, HMGB2 depletion inactivated the NF-κβ signaling in Ang-II-treated VSMCs. Conclusions. Our work demonstrated that inhibition of HMGB2-regulated ferroptosis and inflammation to protect against AAA via NF-κβ signaling, suggesting that HMGB2 may be a potent therapeutic agent for AAA.

中文翻译：

---

HMGB2 缺乏通过 NF-κβ 通路抑制 Ang-II 引起的铁死亡和炎症来减轻腹主动脉瘤

背景。铁死亡是一种新的细胞死亡形式，与多种疾病的发生密切相关。我们的工作重点是 HMGB2 调节腹主动脉瘤 (AAA) 铁死亡和炎症的机制。 方法。利用逆转录定量聚合酶链反应和蛋白质印迹来评估 HMGB2 水平。利用 CCK-8 和流式细胞术测定细胞活力和细胞凋亡。我们检测了 Ang-II 处理的 VSMC 中活性氧的产生、Fe²⁺ 水平和铁死亡相关蛋白水平，这是铁死亡的典型特征。最后建立AAA小鼠模型来验证HMGB2在体内的功能。 结果。在 Ang-II 处理的 VSMC 和 Ang-II 诱导的小鼠模型中观察到 HMGB2 水平增加。 HMGB2 耗竭可加速 Ang-II 刺激的 VSMC 的活力并阻止细胞凋亡。此外，HMGB2 缺陷中和了 Ang-II 引起的 VSMC 中 ROS 的增加。 Fe²⁺ 水平以及 ACSL4 和 COX2 水平的降低以及 GPX4 的增加表明，HMGB2 沉默显着削弱了 Ang-II 引起的 VSMC 铁死亡和 FTH1 级别。此外，shHMGB2 对 Ang-II 诱导的 VSMC 损伤的缓解作用可以被erastin（一种铁死亡激动剂）抵消。从机械角度来看，HMGB2 耗竭使 Ang-II 处理的 VSMC 中的 NF-κβ 信号失活。 结论。我们的工作表明，通过 NF-κβ 信号传导抑制 HMGB2 调节的铁死亡和炎症，从而预防 AAA，这表明 HMGB2 可能是一种有效的治疗剂AAA。