LACC1增强炎症巨噬细胞中的多胺免疫代谢以抑制动脉粥样硬化进展。
LACC1 Enhances Polyamine Immunometabolism in Inflammatory Macrophages to Inhibit Atherosclerosis Progression.
作者信息
Zhang Jingyong, Xu Yuan, Han Zonglin, Liu Bingqi, Wang Maohua, Bao Lili, He Yuxiang
机构信息
Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No.324, Jing five and Wei seven Road, Jinan, 250021, Shandong, China.
Department of Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
出版信息
J Cardiovasc Transl Res. 2025 Apr 28. doi: 10.1007/s12265-024-10585-9.
To explore the function and potential mechanism of laccase domain-containing 1 (LACC1) on atherosclerosis (AS). ApoE mice feed with high-fat diet (HFD) were injected with adenovirus shLACC1 (Ad-shLACC1) or Ad-shNC via tail vein. LACC1 was highly expressed in macrophages of atherosclerotic plaque in ApoE mice and ox-LDL-treated Raw264.7 macrophages. LACC1 silencing enhanced AS development and facilitated inflammation in mice. Then, we found that LACC1 silencing facilitated inflammation but repressed polyamine immunometabolism in ox-LDL-treated Raw264.7 macrophages. Through rescue experiments using ornithine or ODC1 inhibitor (DFMO), we further confirmed that LACC1 promoted polyamine immunometabolism to inhibit inflammation in ox-LDL-treated Raw264.7 macrophages. In addition, the observed LACC1 function was dependent on NOS2. In conclusion, we proved that the downregulation of LACC1 promoted AS progression via inhibiting polyamine immunometabolism in inflammatory macrophages, suggesting LACC1 may be a potential therapeutic target for AS.
探讨含漆酶结构域蛋白1（LACC1）在动脉粥样硬化（AS）中的作用及潜在机制。给喂食高脂饮食（HFD）的载脂蛋白E（ApoE）小鼠经尾静脉注射腺病毒shLACC1（Ad-shLACC1）或Ad-shNC。LACC1在ApoE小鼠动脉粥样硬化斑块的巨噬细胞以及经氧化型低密度脂蛋白（ox-LDL）处理的Raw264.7巨噬细胞中高表达。沉默LACC1可促进小鼠AS发展并加剧炎症。然后，我们发现沉默LACC1可促进经ox-LDL处理的Raw264.7巨噬细胞的炎症，但抑制其多胺免疫代谢。通过使用鸟氨酸或鸟氨酸脱羧酶1（ODC1）抑制剂（二氟甲基鸟氨酸，DFMO）进行挽救实验，我们进一步证实LACC1促进多胺免疫代谢以抑制经ox-LDL处理的Raw264.7巨噬细胞中的炎症。此外，观察到的LACC1功能依赖于一氧化氮合酶2（NOS2）。总之，我们证明LACC1的下调通过抑制炎症巨噬细胞中的多胺免疫代谢促进AS进展，提示LACC1可能是AS的潜在治疗靶点。
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