Open Access

mTOR signaling promotes foam cell formation and inhibits foam cell egress through suppressing the SIRT1 signaling pathway

  • Authors:
    • Haixiang Zheng
    • Yucai Fu
    • Yusheng Huang
    • Xinde Zheng
    • Wei Yu
    • Wei Wang
  • View Affiliations

  • Published online on: July 18, 2017     https://doi.org/10.3892/mmr.2017.7032
  • Pages: 3315-3323
  • Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Atherosclerosis (AS) is a chronic immuno‑inflammatory disease accompanied by dyslipidemia. The authors previously demonstrated that sirtuin 1 (SIRT1) may prevent atherogenesis through influencing the liver X receptor/C‑C chemokine receptor type 7/nuclear factor‑κB (LXR‑CCR7/NF‑κB) signaling pathway. Previous studies have suggested a role for mammalian target of rapamycin (mTOR) signaling in the pathogenesis of cardiovascular diseases. The present study investigated the potential association between mTOR signaling and SIRT1‑LXR‑CCR7/NF‑κB signaling (SIRT1 signaling) in AS pathogenesis. To induce foam cell formation, U937 cells were differentiated into macrophages by exposure to phorbol 12‑myristate 13‑acetate (PMA) for 24 h, followed by treatment with palmitate and oxidized low density lipoprotein for a further 24 h. Oil red O staining revealed a large accumulation of lipid droplets present in foam cells. Western blot analysis demonstrated increased protein levels of phosphorylated (p)‑mTOR and its downstream factor p‑ribosomal protein S6 kinase (p70S6K). Reverse transcription‑quantitative polymerase chain reaction and western blot analyses additionally revealed decreased expression of SIRT1, LXRα and CCR7 and increased expression of NF‑κB and its downstream factor tumor necrosis factor‑α (TNF‑α) in an atherogenetic condition induced by lysophosphatidic acid (LPA). In addition, abundant lipid droplets accumulated in U937‑LPA‑treated foam cells. Rapamycin, an mTOR inhibitor, suppressed the expression and activity of mTOR and p70S6K, however enhanced expression of SIRT1, LXRα, and CCR7. Conversely, rapamycin deceased TNF‑α and NF‑κB activity, the latter of which was further confirmed by immunofluorescence analysis demonstrating increased levels of NF‑κB present in the cytoplasm compared with the nucleus. The findings of the present study suggest that mTOR signaling promotes foam cell formation and inhibits foam cell egress via suppression of SIRT1 signaling.
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September-2017
Volume 16 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Zheng H, Fu Y, Huang Y, Zheng X, Yu W and Wang W: mTOR signaling promotes foam cell formation and inhibits foam cell egress through suppressing the SIRT1 signaling pathway. Mol Med Rep 16: 3315-3323, 2017.
APA
Zheng, H., Fu, Y., Huang, Y., Zheng, X., Yu, W., & Wang, W. (2017). mTOR signaling promotes foam cell formation and inhibits foam cell egress through suppressing the SIRT1 signaling pathway. Molecular Medicine Reports, 16, 3315-3323. https://doi.org/10.3892/mmr.2017.7032
MLA
Zheng, H., Fu, Y., Huang, Y., Zheng, X., Yu, W., Wang, W."mTOR signaling promotes foam cell formation and inhibits foam cell egress through suppressing the SIRT1 signaling pathway". Molecular Medicine Reports 16.3 (2017): 3315-3323.
Chicago
Zheng, H., Fu, Y., Huang, Y., Zheng, X., Yu, W., Wang, W."mTOR signaling promotes foam cell formation and inhibits foam cell egress through suppressing the SIRT1 signaling pathway". Molecular Medicine Reports 16, no. 3 (2017): 3315-3323. https://doi.org/10.3892/mmr.2017.7032