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Article

Atorvastatin attenuates atherosclerotic plaque destabilization by inhibiting endoplasmic reticulum stress in hyperhomocysteinemic mice

  • Authors:
    • Fang Jia
    • Chunfang Wu
    • Zhenyue Chen
    • Guoping Lu
    • Jianhui Sun
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China, Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
  • Pages: 3574-3580
    |
    Published online on: March 3, 2016
       https://doi.org/10.3892/mmr.2016.4975
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Abstract

Endoplasmic reticulum (ER) stress has been suggested to play a role in the progression of plaque vulnerability and the occurrence of acute complications of coronary atherosclerosis. Atorvastatin is known to exert pleiotropic effects on the cardiovascular system. The present study aimed to examine the stabilizing effects of atorvastatin on vulnerable plaques within hyperhomocysteinemic apolipoprotein E‑deficient (ApoE‑/‑) mice, and to investigate the potential mechanisms underlying ER stress in ApoE‑/‑ mice and macrophages. In the present study, ApoE‑/‑ mice were administrated methionine or atorvastatin, and were sacrificed after 2 months. Necrotic core size, collagen content and inflammatory cytokine infiltration were subsequently measured in the aortic lesions, in order to investigate plaque stability. Treatment with atorvastatin decreased the number and size of necrotic cores, increased collagen content, and downregulated tumor necrosis factor (TNF)‑α and matrix metalloproteinase (MMP)‑9 mRNA expression, as compared with the methionine group. Immunohistochemical analysis indicated that atorvastatin administration prevented ER stress activation in aortic lesions of hyperhomocysteinemic mice. Furthermore, macrophages were challenged with homocysteine (Hcy) in the presence or absence of atorvastatin and thapsigargin (an ER stress inducer). Atorvastatin suppressed Hcy‑induced ER stress, and downregulated TNF‑α and MMP‑9 mRNA expression in the macrophages. Conversely, thapsigargin attenuated the inhibitory effects of atorvastatin against Hcy‑induced TNF‑α and MMP‑9 expression. These results indicated that hyperhomocysteinemia may promote atherosclerotic plaque development and instability. In addition, atorvastatin was able to improve atherosclerotic plaque stability in hyperhomocysteinemic mice by inhibiting ER stress.
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Copy and paste a formatted citation
Spandidos Publications style
Jia F, Wu C, Chen Z, Lu G and Sun J: Atorvastatin attenuates atherosclerotic plaque destabilization by inhibiting endoplasmic reticulum stress in hyperhomocysteinemic mice. Mol Med Rep 13: 3574-3580, 2016.
APA
Jia, F., Wu, C., Chen, Z., Lu, G., & Sun, J. (2016). Atorvastatin attenuates atherosclerotic plaque destabilization by inhibiting endoplasmic reticulum stress in hyperhomocysteinemic mice. Molecular Medicine Reports, 13, 3574-3580. https://doi.org/10.3892/mmr.2016.4975
MLA
Jia, F., Wu, C., Chen, Z., Lu, G., Sun, J."Atorvastatin attenuates atherosclerotic plaque destabilization by inhibiting endoplasmic reticulum stress in hyperhomocysteinemic mice". Molecular Medicine Reports 13.4 (2016): 3574-3580.
Chicago
Jia, F., Wu, C., Chen, Z., Lu, G., Sun, J."Atorvastatin attenuates atherosclerotic plaque destabilization by inhibiting endoplasmic reticulum stress in hyperhomocysteinemic mice". Molecular Medicine Reports 13, no. 4 (2016): 3574-3580. https://doi.org/10.3892/mmr.2016.4975
Copy and paste a formatted citation
x
Spandidos Publications style
Jia F, Wu C, Chen Z, Lu G and Sun J: Atorvastatin attenuates atherosclerotic plaque destabilization by inhibiting endoplasmic reticulum stress in hyperhomocysteinemic mice. Mol Med Rep 13: 3574-3580, 2016.
APA
Jia, F., Wu, C., Chen, Z., Lu, G., & Sun, J. (2016). Atorvastatin attenuates atherosclerotic plaque destabilization by inhibiting endoplasmic reticulum stress in hyperhomocysteinemic mice. Molecular Medicine Reports, 13, 3574-3580. https://doi.org/10.3892/mmr.2016.4975
MLA
Jia, F., Wu, C., Chen, Z., Lu, G., Sun, J."Atorvastatin attenuates atherosclerotic plaque destabilization by inhibiting endoplasmic reticulum stress in hyperhomocysteinemic mice". Molecular Medicine Reports 13.4 (2016): 3574-3580.
Chicago
Jia, F., Wu, C., Chen, Z., Lu, G., Sun, J."Atorvastatin attenuates atherosclerotic plaque destabilization by inhibiting endoplasmic reticulum stress in hyperhomocysteinemic mice". Molecular Medicine Reports 13, no. 4 (2016): 3574-3580. https://doi.org/10.3892/mmr.2016.4975
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