Macrophage polarization plays a crucial role in regulating abdominal aortic aneurysm (AAA) formation. Circular RNAs (circRNAs) are important regulators of macrophage polarization during the development of cardiovascular diseases. How-ever, the roles of circRNAs in regulating AAA formation through modulation of macrophage polarization remain unknown. In the present study, we compared circRNA microarray data under two distinct polarizing conditions (M1 and M2 macrophages) and identified an M1-enriched circRNA, circCdyl. Loss- and gain-of-function assay results demonstrated that circCdyl overexpression accelerated angiotensin II (Ang II)- and calcium chloride (CaCl₂)-induced AAA formation by promoting M1 polarization and M1-type inflammation, while circCdyl deficiency showed the opposite effects. RNA pulldown, mass spectrometry analysis, and RNA immunoprecipitation (RIP) assays were conducted to elucidate the underlying mechanisms by which circCdyl regulates AAA formation and showed that circCdyl promotes vascular inflammation and M1 polarization by inhibiting interferon regulatory factor 4 (IRF4) entry into the nucleus, significantly inducing AAA formation. In addition, circCdyl was shown to act as a let-7c sponge, promoting C/EBP-δ expression in macrophages to induce M1 polarization. Our results indicate an important role for circCdyl-mediated macrophage polarization in AAA formation and provide a potent therapeutic target for AAA treatment.

巨噬细胞极化在调节腹主动脉瘤 (AAA) 形成中起着至关重要的作用。环状 RNA (circRNA) 是心血管疾病发展过程中巨噬细胞极化的重要调节因子。然而，circRNA 在通过调节巨噬细胞极化来调节 AAA 形成中的作用仍然未知。在本研究中，我们比较了两种不同极化条件（M1 和 M2 巨噬细胞）下的 circRNA 微阵列数据，并鉴定了富含 M1 的 circRNA，circCdyl。功能丧失和获得测定结果表明，circCdyl 过表达加速了血管紧张素 II (Ang II)- 和氯化钙 (CaCl ₂)-通过促进 M1 极化和 M1 型炎症诱导 AAA 形成，而 circCdyl 缺乏表现出相反的作用。进行 RNA pulldown、质谱分析和 RNA 免疫沉淀 (RIP) 测定以阐明 circCdyl 调节 AAA 形成的潜在机制，并表明 circCdyl 通过抑制干扰素调节因子 4 (IRF4) 进入细胞核促进血管炎症和 M1 极化, 显着诱导 AAA 形成。此外，circCdyl 被证明充当 let-7c 海绵，促进巨噬细胞中 C/EBP-δ 的表达以诱导 M1 极化。我们的结果表明 circCdyl 介导的巨噬细胞极化在 AAA 形成中的重要作用，并为 AAA 治疗提供了有效的治疗靶点。