Modified LDL Particles Activate Inflammatory Pathways in Monocyte-derived Macrophages: Transcriptome Analysis

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Author(s): Alexander N. Orekhov*, Yumiko Oishi , Nikita G. Nikiforov, Andrey V. Zhelankin, Larisa Dubrovsky, Igor A. Sobenin, Alexander Kel, Daria Stelmashenko, Vsevolod J. Makeev, Kathy Foxx, Xueting Jin, Howard S. Kruth, Michael Bukrinsky.

Journal Name: Current Pharmaceutical Design

Abstract:

A hallmark of atherosclerosis is its complex pathogenesis, which is dependent on altered cholesterol metabolism and inflammation. Both arms of pathogenesis involve myeloid cells. Monocytes migrating into the arterial walls interact with modified low-density lipoprotein (LDL) particles, accumulate cholesterol and convert into foam cells, which promote plaque formation and also contribute to inflammation by producing proinflammatory cytokines. A number of studies characterized transcriptomics of macrophages following interaction with modified LDL, and revealed alteration of the expression of genes responsible for inflammatory response and cholesterol metabolism. However, it is still unclear how these two processes are related to each other to contribute to atherosclerotic lesion formation. We attempted to identify the main mater regulator genes in macrophages treated with atherogenic modified LDL using a bioinformatics approach. We found that most of the identified genes were involved in inflammation, and none of them was implicated in cholesterol metabolism. Among the key identified genes were interleukin (IL)-7, IL-7 receptor, IL-15 and CXCL8. Our results indicate that activation of the inflammatory pathway is the primary response of the immune cells to modified LDL, while the lipid metabolism genes may be a secondary response triggered by inflammatory signalling.

Keywords: atherosclerosis, inflammation, macrophages, LDL, modified LDL, pro-inflammatory signaling

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(E-pub Ahead of Print)
DOI: 10.2174/1381612824666180911120039

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