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• W3183859963 abstract "Atherosclerosis (AS), characterized by cholesterol overloaded-macrophages accumulation and plaque formation in blood vessels, is the major cause of cardiovascular disease. Transactive response DNA-binding protein∼43 kDa (TDP43) has recently been identified as an independent driver of neurodegenerative diseases through triggering inflammatory response. This study investigated whether TDP43 is involved in AS development, especially in macrophages-mediated-foam cell formation and inflammatory responses.Transactive response DNA-binding protein∼43 kDa expressions in oxidized low-density lipoprotein (oxLDL)-treated macrophages and peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD) were detected by real time-polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence. Gene gain or loss of function was used to investigate the effects of TDP43 on macrophages-mediated lipid untake and inflammation with ELISA, protein immunoprecipitation, RT-PCR, Western blot, and immunofluorescence. Macrophage TDP43 specific knockout mice with ApoE-/- background were fed with western diet for 12 weeks to establish AS model, and used to explore the role of TDP43 on AS progression.Transactive response DNA-binding protein∼43 kDa expression increases in oxLDL-treated macrophages and PBMCs from patients with CAD. Furthermore, we find that TDP43 promotes activation of NF-κB to increase inflammatory factor expression in macrophages through triggering mitochondrial DNA release to activate cGAS-STING signaling. Moreover, TDP43 strengthens lipid uptake of macrophages through regulating β-catenin and PPAR-γ complex to promote scavenger receptor gene CD36 transcription. Finally, using macrophage TDP43 specific knockout mice with ApoE-/- background fed with western diet for 12 weeks to establish AS model, we find that specific knockout of TDP43 in macrophages obviously alleviates western diet-induced AS progression in mice.Transactive response DNA-binding protein∼43 kDa exacerbates atherosclerosis progression by promoting inflammation and lipid uptake of macrophages, suggesting TDP43 as a potential target for developing atherosclerotic drug." @default.
• W3183859963 created "2021-08-02" @default.
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• W3183859963 date "2021-07-05" @default.
• W3183859963 modified "2023-10-13" @default.
• W3183859963 title "TDP43 Exacerbates Atherosclerosis Progression by Promoting Inflammation and Lipid Uptake of Macrophages" @default.
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• W3183859963 doi "https://doi.org/10.3389/fcell.2021.687169" @default.
• W3183859963 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8287832" @default.
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• W3183859963 hasPublicationYear "2021" @default.
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