ATF3 (activating transcription factor 3) is a member of the mammalian activation transcription factor/cAMP-responsive element-binding (CREB) family. It plays a role in inflammation and innate immunity, and suggests that ATF3 is associated with atherosclerosis. In our study, we analyzed datasets of atherosclerosis from the NCBI-GEO (Gene Expression Omnibus) database and found that expression levels of ATF3 were lower in macrophages from ruptured atherosclerotic plaques than from stable atherosclerotic plaques. Expression levels of ATF3 correlated with the stability of atherosclerotic plaques. KEGG analysis of different expression genes (DEGs) between ruptured and stable atherosclerotic plaques was performed by Metascape database. The PI3K-AKT pathway may be a potential pathway of the formation of ruptured atherosclerotic plaques. High-fat diet-induced atherosclerosis apoE^−/− mice were divided into two groups: a model group and an ATF3 overexpression (OE)-group. Tests on atherosclerotic plaques in the aortic root suggested that absence of ATF3 and increase of macrophages may be risk factors for the formation of ruptured atherosclerotic plaques. We found decreased areas of lesions in aortic roots and branches of aortic arch, as well as increased lesional content of macrophages as well as TUNEL-positive areas. Consistent with these results, we found reduced degradation and incidence of elastic plate cracks accompanied by suppressed MMPs expression and transduction pathway protein PI3K/AKT activation. These data suggest that ATF3 is a signaling molecule that mediates the progression and stability of atherosclerotic plaques. ATF3 could be a potential new biomarker for the prognosis of atherosclerosis and may be a therapeutic target to reduce atherosclerosis.

ATF3（激活转录因子 3）是哺乳动物激活转录因子/cAMP 响应元件结合 (CREB) 家族的成员。它在炎症和先天免疫中发挥作用，表明 ATF3 与动脉粥样硬化有关。在我们的研究中，我们分析了 NCBI-GEO（基因表达综合）数据库中的动脉粥样硬化数据集，发现破裂的动脉粥样硬化斑块的巨噬细胞中 ATF3 的表达水平低于稳定的动脉粥样硬化斑块的巨噬细胞。 ATF3 的表达水平与动脉粥样硬化斑块的稳定性相关。通过Metascape数据库对破裂和稳定动脉粥样硬化斑块之间的不同表达基因（DEG）进行KEGG分析。 PI3K-AKT途径可能是破裂动脉粥样硬化斑块形成的潜在途径。高脂饮食诱导的动脉粥样硬化apoE ^−/−小鼠被分为两组：模型组和ATF3过表达（OE）组。对主动脉根部动脉粥样硬化斑块的测试表明，ATF3 的缺失和巨噬细胞的增加可能是动脉粥样硬化斑块破裂形成的危险因素。我们发现主动脉根部和主动脉弓分支病变面积减少，巨噬细胞和TUNEL阳性区域的病变含量增加。与这些结果一致，我们发现弹性板裂纹的降解和发生率降低，同时 MMP 表达和转导途径蛋白 PI3K/AKT 激活受到抑制。这些数据表明ATF3是介导动脉粥样硬化斑块进展和稳定性的信号分子。 ATF3可能是动脉粥样硬化预后的潜在新生物标志物，并且可能是减少动脉粥样硬化的治疗靶点。