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  • Title: Oxidized LDL Disrupts Metabolism and Inhibits Macrophage Survival by Activating a miR-9/Drp1/Mitochondrial Fission Signaling Pathway.
    Author: Xin T, Lu C, Zhang J, Wen J, Yan S, Li C, Zhang F, Zhang J.
    Journal: Oxid Med Cell Longev; 2020; 2020():8848930. PubMed ID: 33204400.
    Abstract:
    Mitochondrial dysfunction is associated with macrophage damage, but the role of mitochondrial fission in macrophage cholesterol metabolism is not fully understood. In this study, we explored the influences of miR-9 and mitochondrial fission on macrophage viability and cholesterol metabolism. Macrophages were incubated with oxidized low-density lipoprotein (ox-LDL) in vitro, after which mitochondrial fission, cell viability, and cholesterol metabolism were examined using qPCR, ELISAs, and immunofluorescence. ox-LDL treatment significantly increased Drp1-associated mitochondrial fission. Transfection of Drp1 siRNA significantly reduced cell death, attenuated oxidative stress, and inhibited inflammatory responses in ox-LDL-treated macrophages. Interestingly, inhibition of Drp1-related mitochondrial fission also improved cholesterol metabolism by balancing the transcription of cholesterol influx/efflux enzymes. We also found that miR-9 was downregulated in ox-LDL-treated macrophages, and administration of a miR-9 mimic decreased Drp1 transcription and mitochondrial fission, as well as its effects. These results indicate that signaling via the novel miR-9/Drp1/mitochondrial fission axis is a key determinant of macrophage viability and cholesterol metabolism.
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