title: SIRT1 prevents atherosclerosis via liver‑X‑receptor and NF‑κB signaling in a U937 cell model.
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.
authors: Department of Cardiology, Second Afﬁliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, PR China.
authors: Hai-Tao
authors: HT
authors: Zeng
authors: Yu-Cai
authors: YC
authors: Fu
authors: Wei
authors: W
authors: Yu
authors: Jun-Ming
authors: JM
authors: Lin
authors: Liang
authors: L
authors: Zhou
authors: Lei
authors: L
authors: Liu
authors: Wei
authors: W
authors: Wang
mesh_terms: D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D000071518:Liver X Receptors; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D020298:U937 Cells
chemical_list: D000071518:Liver X Receptors; D016328:NF-kappa B; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D010168:Palmitates; D012333:RNA, Messenger; D014280:Triglycerides; D056564:Sirtuin 1