LACC1 Enhances Polyamine Immunometabolism in Inflammatory Macrophages to Inhibit Atherosclerosis Progression.

IF 2.4 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of Cardiovascular Translational Research Pub Date : 2025-04-28 DOI:10.1007/s12265-024-10585-9

Jingyong Zhang, Yuan Xu, Zonglin Han, Bingqi Liu, Maohua Wang, Lili Bao, Yuxiang He

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Abstract

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.

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LACC1增强炎性巨噬细胞多胺免疫代谢抑制动脉粥样硬化进展

探讨漆酶结构域1 （LACC1）在动脉粥样硬化（AS）中的作用及其潜在机制。采用高脂饲料（HFD）喂养ApoE-/-小鼠，通过尾静脉注射腺病毒shLACC1 （Ad-shLACC1）或Ad-shNC。在ApoE-/-小鼠和ox- ldl处理的Raw264.7巨噬细胞中，LACC1在动脉粥样硬化斑块巨噬细胞中高表达。LACC1沉默可增强小鼠AS的发展并促进炎症。然后，我们发现LACC1沉默促进了ox- ldl处理的Raw264.7巨噬细胞的炎症，但抑制了多胺免疫代谢。通过鸟氨酸或ODC1抑制剂（DFMO）的救援实验，我们进一步证实LACC1促进多胺免疫代谢，抑制ox- ldl处理的Raw264.7巨噬细胞的炎症。此外，观察到的LACC1功能依赖于NOS2。总之，我们证明LACC1的下调通过抑制炎性巨噬细胞多胺免疫代谢促进AS的进展，提示LACC1可能是AS的潜在治疗靶点。

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来源期刊

Journal of Cardiovascular Translational Research CARDIAC & CARDIOVASCULAR SYSTEMS-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

6.10

自引率

2.90%

发文量

148

审稿时长

6-12 weeks

期刊介绍： Journal of Cardiovascular Translational Research (JCTR) is a premier journal in cardiovascular translational research. JCTR is the journal of choice for authors seeking the broadest audience for emerging technologies, therapies and diagnostics, pre-clinical research, and first-in-man clinical trials. JCTR''s intent is to provide a forum for critical evaluation of the novel cardiovascular science, to showcase important and clinically relevant aspects of the new research, as well as to discuss the impediments that may need to be overcome during the translation to patient care.