ATF3通过 NF-κκκB 信号通路调控动脉粥样硬化斑块内的炎症反应

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Abstract：Objective To investigate theroleofactivatingtranscriptionfactor3（ATF3）inatherosclerotic plaquesforregulating inflammatory responses during atherosclerosis （AS）progression. Methods Human coronary artery specimens fromautopsy cases wereexaminedfor ATF3 protein expresionandlocalizationusing immunofluorescence stainingand Westernbloting. Apolipoprotein E-deficient （ApoE-1 ）mouse models of AS induced by high-fat diet （HFD） feeding for12 weekswere subjected totailveininjectionofadenoassiatedviusserotye9（AAV9）toknockdownATF3expression.Afteranadditional5weeks of HFDfeedingthemice wereeuthanizedforanalyzingstructuralchangesof theaorticplaques，andtheexpresionlevelsof ATF3，inmmaoryctors（45，68，I-1β，F- α ），andN- ⋅κB pathwayproteins P-lKKα/β andP-NF-κB p65）were detected.Intecellexperiment，TH--erivedfamcelsweretransfecedwithanA3overexpresingplasmidospecificsiRNAtovalidatetherelationshipbetweenATF3andNF-kBsignaling.ResultsInhumanatheroscleroticplaques， ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE-/- mice significantly increasedaortic plaque volume， upregulated the inflammatory factors，enhanced phosphorylationof the NF-kB pathway proteins，andincreasedtheexpresionsofVCAM1，MMP9，andMMP2 intheplaques.InHP-1-derived foamcels3 silencingcausedactivationoftheN-BpathwaywhileAT3overexpressionsuppressedtheactivityoftheNF-pathay. Conclusion AS promotes ATF3 expression，and ATF3 deficiency exacerbates AS progresson by enhancing plaque inflammation viaactivating theNF-kB pathway，suggesting the potential ofATF3asatherapeutic target for AS. Keywords：atherosclerosis;activating transcriptionfactor3;inflammatoryresponse;nuclearfactor-B;suddencardiacdeath

冠状动脉粥样硬化性心脏病（CHD）是全球非传染性疾病死亡的头号杀手，所致全球死亡人数占全球总死亡人数的 16% ，且呈逐年增高的趋势[1]。（剩余15771字）