Cardiovascular Drugs and Therapy

, Volume 26, Issue 1, pp 23–30 | Cite as

Simvastatin Suppresses Apoptosis in Vulnerable Atherosclerotic Plaques Through Regulating the Expression of p53, Bcl-2 and Bcl-xL

  • Weiwei Qin
  • Yonggang Lu
  • Chengyan Zhan
  • Tao Shen
  • Lin Dou
  • Yong Man
  • Shu Wang
  • Chuanshi Xiao
  • Yunfei Bian
  • Jian Li



Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has antioxidant and anti-inflammatory properties that are independent of lipid-lowering abilities. This experiment was carried out to explore the effects of simvastatin on apoptosis in vulnerable atherosclerotic plaques of apoE-deficient mice.

Methods and results

Eight weeks-old apoE−/− mice were fed a Western-type diet. Vulnerable atherosclerotic lesions were formed in the branchiocephalic artery at the age of 30-weeks, before simvastatin administration for 8 weeks. Simvastatin did neither affect the levels of plasma glucose and lipids, nor the size of atherosclerotic lesions. Analysis of plaque composition showed that simvastatin decreased the area of lipid core and increased the amounts of macrophages and smooth muscle cells in atherosclerotic plaques of apoE−/− mice. In addition, simvastatin down-regulated the expression of vascular cell adhesion molecule-1 (VCAM-1) by both inhibition of nuclear factor kappa B (NF-кB) activation and suppression of the expression of the receptor for advanced glycation end products (RAGE). Moreover, we found that simvastatin administration led to reduced TUNEL-positive cells in the aortic root lesions, accompanied by up-regulation of Bcl-2 and Bcl-xL expression, and decreased P53 expression as shown by Western blot.


In the present study, we show novel data to suggest that simvastatin could suppress apoptosis in vulnerable atherosclerotic plaques of apoE−/− mice by regulating the expression of apoptosis-related proteins, such as p53, Bcl-2 and Bcl-xL.

Key words

Simvastatin Vulnerable lesions Apoptosis Bcl-2 Bcl-xL p53 



This work was supported by grants from National Basic Research Program of China (2012CB517502) and National Natural Science Foundation of China (81070634).

Conflict of interest

None declared.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Weiwei Qin
    • 1
    • 2
  • Yonggang Lu
    • 1
  • Chengyan Zhan
    • 3
  • Tao Shen
    • 1
  • Lin Dou
    • 1
  • Yong Man
    • 1
  • Shu Wang
    • 1
  • Chuanshi Xiao
    • 2
  • Yunfei Bian
    • 2
  • Jian Li
    • 1
  1. 1.The Key Laboratory of GeriatricsBeijing Hospital & Beijing Institute of Geriatrics, Ministry of HealthBeijingChina
  2. 2.The Second Hospital of Shanxi Medical UniversityTaiyuanChina
  3. 3.Shanghai PuNan HospitalShanghaiChina

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