南方医科大学学报2025，Vol.45Issue(6)：1131-1142,12.DOI:10.12122/j.issn.1673-4254.2025.06.03
ATF3通过NF-κB信号通路调控动脉粥样硬化斑块内的炎症反应
ATF3 regulates inflammatory response in atherosclerotic plaques in mice through the NF-κB signaling pathway
摘要
Abstract
Objective To investigate the role of activating transcription factor 3(ATF3)in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis(AS)progression.Methods Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting.Apolipoprotein E-deficient(ApoE-/-)mouse models of AS induced by high-fat diet(HFD)feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9(AAV9)to knock down ATF3 expression.After an additional 5 weeks of HFD feeding,the mice were euthanized for analyzing structural changes of the aortic plaques,and the expression levels of ATF3,inflammatory factors(CD45,CD68,IL-1β,and TNF-α),and NF-κB pathway proteins(P-IKKα/β and P-NF-κB p65)were detected.In the cell experiment,THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF-κB signaling.Results In human atherosclerotic plaques,ATF3 expression was significantly elevated and partially co-localized with CD68.ATF3 knockout in ApoE-/-mice significantly increased aortic plaque volume,upregulated the inflammatory factors,enhanced phosphorylation of the NF-κB pathway proteins,and increased the expressions of VCAM1,MMP9,and MMP2 in the plaques.In THP-1-derived foam cells,ATF3 silencing caused activation of the NF-κB pathway,while ATF3 overexpression suppressed the activity of the NF-κB pathway.Conclusion AS promotes ATF3 expression,and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway,suggesting the potential of ATF3 as a therapeutic target for AS.关键词
动脉粥样硬化/转录激活因子3/炎症反应/NF-κB/冠心病猝死Key words
atherosclerosis/activating transcription factor 3/inflammatory response/nuclear factor-κB/sudden cardiac death引用本文复制引用
夏冰,彭进,丁九阳,王杰,唐国伟,刘国杰,王沄,万昌武,乐翠云..ATF3通过NF-κB信号通路调控动脉粥样硬化斑块内的炎症反应[J].南方医科大学学报,2025,45(6):1131-1142,12.基金项目
国家自然科学基金(82460335) （82460335）
贵州省科技计划项目(黔科合基础-ZK[2022]一般357) Supported by National Natural Science Foundation of China(82460335). （黔科合基础-ZK[2022]一般357）
