SIRT1 agonist inhibits smooth muscle foam cell formation by decreasing ACAT1 expression

Xu Wang; Xue Chen; Mengjiao Sun; Mingjie Zhang; Lu Guo; Jie Zhu; Jingcheng Li; Lili Zhang

doi:10.16016/j.1000-5404.201611076

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SIRT1 agonist inhibits smooth muscle foam cell formation by decreasing ACAT1 expression

更新时间：2026-01-09

- SIRT1 agonist inhibits smooth muscle foam cell formation by decreasing ACAT1 expression
- Journal of Third Military Medical University Vol. 39, Issue 9, Pages: 846-851(2017)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81471193);the Youth Talent Plan for Scientific and Technological Innovation of General Hospital of Chengdu Military Command(2016KC01)
- DOI：10.16016/j.1000-5404.201611076
  CLC：
- Received：16 November 2016，
  
  Published：15 May 2017
- 稿件说明：
移动端阅览
Xu Wang, Xue Chen, Mengjiao Sun, et al. SIRT1 agonist inhibits smooth muscle foam cell formation by decreasing ACAT1 expression[J]. Journal of Third Military Medical University, 2017, 39(9): 846-851.
DOI：

Xu Wang, Xue Chen, Mengjiao Sun, et al. SIRT1 agonist inhibits smooth muscle foam cell formation by decreasing ACAT1 expression[J]. Journal of Third Military Medical University, 2017, 39(9): 846-851. DOI： 10.16016/j.1000-5404.201611076.

摘要

Abstract

Objective

To determine the effect of silent information regulation 2 homolog-1 (SIRT1) on foam cell formation in vascular smooth muscle cell (VSMC) after the inducement of oxidized low density lipoprotein (ox-LDL) and investigate the underlying mechanisms.

Methods

Primary VSMC were isolated from the aorta of male C57BL/6J mice and identified by immunofluorescence staining. The VSMC-derived foam cell formation was induced by the stimulation of 80 μg/mL ox-LDL for 24

48 or 72 h. The expression profile of SIRT1 was measured in the process of foam cell formation. SIRT1 agonist SRT1720 (SRT

1 μmol/L) and its antagonist nicotinamide (Nic

100 μmol/L) were used as well. Western blotting was employed to measure the protein expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and acyl-coenzyme a: A-cholesterol acyltransferase 1 (ACAT1). Oil red O staining was used to detect intracellular lipid deposition and foam cell formation. PPARγ agonist rosiglitazone (RSG

50 μmol/L) and its inhibitor GW9662 (10 μmol/L) were used to manipulate the activity of PPARγ

and their effects on the expression of ACAT1 were detected by Western blotting.

Results

① The expression of SIRT1 in VSMC-derived foam cells was reduced approximately by 47% after 48 hours'

ox-LDL incubation (

0.01). Oil red O staining showed that SRT+ox-LDL treatment inhibited the formation of VSMC-derived foam cells

while the stimulation of SIRT1 antagonist Nic reversed such effect. ② The expression level of ACAT1 was enhanced in the VSMC-derived foam cells (2.77±0.70

0.01)

which could be counteracted by SRT (0.90±0.27

0.01). However

Nic stimulation resulted in block in the inhibition and enhanced the expression of ACAT1 (2.25±0.37

0.05). ③ The expression of PPARγ was decreased in the VSMC after ox-LDL stimulation (0.73±0.09

0.01). SIRT1 agonist SRT significantly up-regulated the expression (0.98±0.16

0.05)

while Nic down-regulated (0.47±0.13

0.01). ④ PPARγ agonist RSG suppressed the expression of ACAT1 in VSMC-derived foam cells (0.73±0.09

0.01)

while the inhibitor GW9662 increased the expression (1.68±0.09

0.01).

Conclusion

SIRT1 inhibits the expression of ACAT1 induced by ox-LDL through up-regulating PPARγ

and thus ultimately suppresses the foam cell formation in VSMC.

关键词

Keywords

references

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