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previous studies have shown that the resulting compound of this reaction, isopentenyl diphosphate (IPP), can be exported to the extracellular space by DCs using the cholesterol efflux transporter ABCA1 and this serves as an indicator of hyperactive mevalonate metabolism that alerts the immune system ( Figures 3A, C ) is also interesting and in line with recent reports showing that the mTOR-driven metabolic reprogramming of macrophages increased flux through the mevalonate pathway and this process is involved in trained immunity ( LDLR gene encoding for the LDL receptor was the top significant upregulated gene and more studies are needed to evaluate its role as a cell surface sensor or innate receptor in response to Al-CPI or whether it is implicated in the transcriptional changes of sterol metabolic genes
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