SIRT1 prevents atherosclerosis via liver‑X‑receptor and NF‑κB signaling in a U937 cell model

Zeng,Hai‑Tao; Fu,Yu‑Cai; Yu,Wei; Lin,Jun‑Ming; Zhou,Liang; Liu,Lei; Wang,Wei

doi:10.3892/mmr.2013.1460

SIRT1 prevents atherosclerosis via liver‑X‑receptor and NF‑κB signaling in a U937 cell model

Authors:
- Hai‑Tao Zeng
- Yu‑Cai Fu
- Wei Yu
- Jun‑Ming Lin
- Liang Zhou
- Lei Liu
- Wei Wang
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Affiliations: Department of Cardiology, Second Afﬁliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China, Laboratory of Cell Senescence, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
Published online on: May 8, 2013 https://doi.org/10.3892/mmr.2013.1460
Pages: 23-28

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Abstract

Atherosclerosis is a chronic immunoinﬂammatory disease associated with blood lipid disorders. Previous studies in mice have demonstrated that liver X receptor (LXR)‑ATP‑binding cassette (ABC) A1/ABCG1/C‑C chemokine receptor type 7 (CCR7) and nuclear factor κB (NF‑κB) signaling pathways are important for atherosclerotic plaque formation. In addition, Sirtuin 1 (SIRT1) has been reported as a key regulator in the protection from risk of atherosclerosis. However, the exact mechanism by which SIRT1 prevents atherosclerosis remains largely unknown. To explore the possible mechanisms, the expression of SIRT1 and the association between SIRT1, LXR and NF‑κB in the process of foam cell formation was investigated in an in vitro human mononuclear U937 cell line. Monocyte‑derived foam cells were induced by palmitate and Ox‑LDL treatment. Oil Red O staining revealed an accumulation of a large number of lipid droplets in foam cells. Results of reverse transcription polymerase chain reaction (RT-PCR) revealed that SIRT1 expression was downregulated during foam cell formation. In addition, the expression of LXRα and its targets, ABCA1, ABCG1 and CCR7, were downregulated. However, NF‑κB and its targets, tumor necrosis factor α (TNFα) and interleukin (IL)‑1β, were upregulated in foam cells. Following activation of SIRT1 by SRT1720, the expression of LXRα and its targets increased, whereas expression of NF‑κB and its targets decreased. Furthermore, the formation of foam cells was blocked. The SIRT1 inhibitor, nicotinamide, was found to eliminate the effects of SRT1720. Results of the present study indicate that SIRT1 may prevent the formation and progression of atherosclerosis by enhancing the LXR‑ABCA1/ABCG1/CCR7 and inhibiting the NF‑κB pathways.

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