课题组前期研究证实，干扰素调节因子-1（IRF-1）促进急性冠脉综合征（ACS）患者巨噬细胞焦亡并在动脉粥样硬化（AS）中发挥重要作用，但调控机制有待阐明。预实验发现ACS患者单核细胞来源的巨噬细胞中hsa_circ_0029589表达显著降低，而其m6A水平及甲基化转移酶METTL3表达明显升高；IRF-1可显著抑制ACS患者巨噬细胞hsa_circ_0029589的表达并上调其m6A水平；沉默METTL3后，hsa_circ_0029589表达恢复，而巨噬细胞焦亡明显减轻。因此我们提出：IRF-1在AS中可通过调控circ_0029589的m6A修饰促进巨噬细胞焦亡。本研究拟通过在体及体外实验观察：1）AS中IRF-1的表达规律及其与circ_0029589表达、巨噬细胞焦亡的关系；2）IRF-1通过调控circ_0029589的m6A修饰促进巨噬细胞焦亡在AS的作用及机制。

We found that Interferon regulatory factor-1 (IRF-1) could promote macrophage pyroptosis in patients with acute coronary syndrome (ACS), which play an important role in atherosclerosis (AS); however, the regulatory mechanism remains unknown. Our preliminary experiment revealed that the relative expression of hsa_circ_0029589 was decreased, whereas the N6-methyladenosine (m6A) level of hsa_circ_0029589 and the expression of m6A methyltransferase METTL3 were significantly elevated in macrophages in patients with ACS; IRF-1 suppressed hsa_circ_0029589 expression but upregulated its m6A level; additionally, inhibition of METTL3 increased the expression of hsa_circ_0029589 and attenuated macrophage pyroptosis. Therefore, we propose that IRF-1 promote macrophage pyroptosis in atherosclerosis by modulating m6A modification of circ_0029589. We will dynamically investigate: 1) the expression of IRF-1 and its relationship with the expression of circ_0029589, macrophage pyroptosis and inflammation in AS; 2) the role and mechanism of IRF-1 promoting macrophage pyroptosis in atherosclerosis by modulating m6A modification of circ_0029589.