Background and Purpose. Abdominal aortic aneurysm (AAA) is a chronic inflammatory disorder and the important causes of death among men over the age of 65 years. Interleukin-12p35 (IL12p35) is an inflammatory cytokine that participates in a variety of inflammatory diseases. However, the role of IL12p35 in the formation and development of AAA is still unknown. Experimental Approach. Male apolipoprotein E-deficient (Apoe^-/-) mice were generated and infused with 1.44 mg/kg angiotensin II (Ang II) per day. We found that IL12p35 expression was noticeably increased in the murine AAA aorta and isolated aortic smooth muscle cells (SMCs) after Ang II stimulation. IL12p35 silencing promoted Ang II-induced AAA formation and rupture in Apoe^-/- mice. IL12p35 silencing markedly increased the expression of inflammatory cytokines, including IL-1β, IL-6, and tumor necrosis factor-α (TNF-α), in both the serum and AAA aorta. Additionally, IL12p35 silencing exacerbated SMC apoptosis in Apoe^-/- mice after Ang II infusion. IL12p35 silencing significantly increased signal transducer and activator of transcription (STAT) 4 phosphorylation levels in AAA mice, and STAT4 knockdown abolished the IL12p35-mediated proinflammatory response and SMC apoptosis. Interpretation. Silencing IL12p35 promotes AAA formation by activating the STAT4 pathway, and IL12p35 may serve as a novel and promising therapeutic target for AAA treatment.

中文翻译：

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沉默 IL12p35 通过激活 STAT4 通路促进血管紧张素 II 介导的腹主动脉瘤

背景和目的。腹主动脉瘤（AAA）是一种慢性炎症性疾病，是 65 岁以上男性死亡的重要原因。白细胞介素12p35（IL12p35）是一种炎症细胞因子，参与多种炎症性疾病。然而，IL12p35 在 AAA 的形成和发展中的作用仍然未知。实验方法。产生雄性载脂蛋白 E 缺陷 (Apoe ^-/- ) 小鼠并每天输注 1.44 mg/kg 血管紧张素 II (Ang II)。我们发现在 Ang II 刺激后，小鼠 AAA 主动脉和分离的主动脉平滑肌细胞 (SMC) 中的 IL12p35 表达显着增加。IL12p35 沉默促进 Apoe 中 Ang II 诱导的 AAA 形成和破裂^-/-老鼠。IL12p35 沉默显着增加了血清和 AAA 主动脉中炎性细胞因子的表达，包括 IL-1 β、IL-6 和肿瘤坏死因子-α (TNF -α )。此外，在 Ang II 输注后，IL12p35 沉默加剧了 Apoe ^-/-小鼠的 SMC 凋亡。IL12p35 沉默显着增加了 AAA 小鼠的信号转导和转录激活因子 (STAT) 4 磷酸化水平，而 STAT4 敲低消除了 IL12p35 介导的促炎反应和 SMC 凋亡。解释。沉默 IL12p35 通过激活 STAT4 通路促进 AAA 形成，IL12p35 可作为 AAA 治疗的新型且有希望的治疗靶点。