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Article

Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway

  • Authors:
    • Shiping Cao
    • Zhi Zeng
    • Xianbao Wang
    • Jianping Bin
    • Dingli Xu
    • Yulin Liao
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Organ Failure Key Laboratory of the Ministry of Education, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
  • Pages: 1163-1168
    |
    Published online on: August 9, 2013
       https://doi.org/10.3892/mmr.2013.1622
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Abstract

Tumor necrosis factor‑α (TNF-α) and c‑Jun N‑terminal kinases (JNKs) are known to be associated with apoptosis and are important in cardiac remodeling. It remains to be determined whether statins inhibit cardiac remodeling through interfering with TNF‑α‑JNK‑related signaling pathways. This study was designed to investigate the effect of pravastatin on the progression of hypertrophy to heart failure in transverse aortic constriction (TAC) and the associations with TNF‑α‑JNK signaling. Either pravastatin (5 or 20 mg/kg/day) or vehicle was orally administered to male C57BL/6J mice with TAC. Cardiac remodeling and left ventricular hemodynamics, as well as JNK-dependent apoptotic signals were analyzed 4 weeks following TAC. Neonatal rat cardiomyocytes were cultured to investigate the effect of pravastatin on TNF‑α‑induced JNK‑related apoptotic signals. Notably, pravastatin reduced the heart/body weight and lung/body weight ratios. In addition, a decrease of left ventricular (LV) echocardiographic dimensions, an increase of LV fractional shortening and diastolic index, a reduction of JNK activity, caspase‑12 and Bax were observed in the pravastatin‑treated groups. The TNF‑α‑induced phosphorylation of JNK and upregulation of caspase‑12 and Bax in cultured cardiomyocytes was inhibited by pravastatin. These results indicated that pravastatin attenuates cardiac remodeling by inhibiting JNK‑dependent pro‑apoptotic signaling.
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Copy and paste a formatted citation
Spandidos Publications style
Cao S, Zeng Z, Wang X, Bin J, Xu D and Liao Y: Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway. Mol Med Rep 8: 1163-1168, 2013.
APA
Cao, S., Zeng, Z., Wang, X., Bin, J., Xu, D., & Liao, Y. (2013). Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway. Molecular Medicine Reports, 8, 1163-1168. https://doi.org/10.3892/mmr.2013.1622
MLA
Cao, S., Zeng, Z., Wang, X., Bin, J., Xu, D., Liao, Y."Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway". Molecular Medicine Reports 8.4 (2013): 1163-1168.
Chicago
Cao, S., Zeng, Z., Wang, X., Bin, J., Xu, D., Liao, Y."Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway". Molecular Medicine Reports 8, no. 4 (2013): 1163-1168. https://doi.org/10.3892/mmr.2013.1622
Copy and paste a formatted citation
x
Spandidos Publications style
Cao S, Zeng Z, Wang X, Bin J, Xu D and Liao Y: Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway. Mol Med Rep 8: 1163-1168, 2013.
APA
Cao, S., Zeng, Z., Wang, X., Bin, J., Xu, D., & Liao, Y. (2013). Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway. Molecular Medicine Reports, 8, 1163-1168. https://doi.org/10.3892/mmr.2013.1622
MLA
Cao, S., Zeng, Z., Wang, X., Bin, J., Xu, D., Liao, Y."Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway". Molecular Medicine Reports 8.4 (2013): 1163-1168.
Chicago
Cao, S., Zeng, Z., Wang, X., Bin, J., Xu, D., Liao, Y."Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway". Molecular Medicine Reports 8, no. 4 (2013): 1163-1168. https://doi.org/10.3892/mmr.2013.1622
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