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Article

Mammalian target of rapamycin overexpression antagonizes chronic hypoxia-triggered pulmonary arterial hypertension via the autophagic pathway

  • Authors:
    • Lingxia Li
    • Xiaochuang Wang
    • Lina Wang
    • Li Qu
    • Xinye Zhu
    • Manxiang Li
    • Xiaoyan Dang
    • Ping Li
    • Yanxia Gao
    • Zhuo Peng
    • Longfei Pan
    • Li Wan
  • View Affiliations / Copyright

    Affiliations: The Cadre Ward, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Emergency Medicine, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Respiratory Diseases, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
  • Pages: 316-322
    |
    Published online on: May 26, 2015
       https://doi.org/10.3892/ijmm.2015.2224
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Abstract

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disorder with high morbidity and mortality, and is characterized by excessive growth of endothelial cells. Recently, the mammalian target of rapamycin (mTOR) has attracted increasing attention due to its potential as a therapeutic target against certain diseases associated with proliferative and metabolic abnormalities. However, the effect on mTOR on PAH has not yet been elucidated. In the present study, a marked downregulation of mTOR was observed in PAH patients. Following construction of a mouse model of PAH by chronic exposure to hypoxia, adenovirus-mediated upregulation of mTOR significantly attenuated right ventricular systolic pressure, right ventricular hypertrophy and wall thickness of pulmonary arterioles, indicating a protective effect of mTOR on PAH. Further analysis confirmed that mTOR overexpression inhibited autophagy triggered by hypoxia through blocking light chain 3 II expression and increasing p62 levels. In vitro, hypoxia enhanced the proliferation of human pulmonary artery endothelial cells (PAECs), which was markedly abrogated by mTOR overexpression. Of note, upregulation of mTOR inhibited the hypoxia-induced autophagy pathway, which contributed to cell proliferation, while silencing of autophagy by RNA interference with ATG5 significantly inhibited cell proliferation. In conclusion, the results of the present study suggested a potential protective effect of mTOR on the progression of PAH by suppressing PAEC proliferation through blocking the autophagic pathway. Therefore, the present study suggested that mTOR is a promising therapeutic agent against PAH.
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Copy and paste a formatted citation
Spandidos Publications style
Li L, Wang X, Wang L, Qu L, Zhu X, Li M, Dang X, Li P, Gao Y, Peng Z, Peng Z, et al: Mammalian target of rapamycin overexpression antagonizes chronic hypoxia-triggered pulmonary arterial hypertension via the autophagic pathway. Int J Mol Med 36: 316-322, 2015.
APA
Li, L., Wang, X., Wang, L., Qu, L., Zhu, X., Li, M. ... Wan, L. (2015). Mammalian target of rapamycin overexpression antagonizes chronic hypoxia-triggered pulmonary arterial hypertension via the autophagic pathway. International Journal of Molecular Medicine, 36, 316-322. https://doi.org/10.3892/ijmm.2015.2224
MLA
Li, L., Wang, X., Wang, L., Qu, L., Zhu, X., Li, M., Dang, X., Li, P., Gao, Y., Peng, Z., Pan, L., Wan, L."Mammalian target of rapamycin overexpression antagonizes chronic hypoxia-triggered pulmonary arterial hypertension via the autophagic pathway". International Journal of Molecular Medicine 36.1 (2015): 316-322.
Chicago
Li, L., Wang, X., Wang, L., Qu, L., Zhu, X., Li, M., Dang, X., Li, P., Gao, Y., Peng, Z., Pan, L., Wan, L."Mammalian target of rapamycin overexpression antagonizes chronic hypoxia-triggered pulmonary arterial hypertension via the autophagic pathway". International Journal of Molecular Medicine 36, no. 1 (2015): 316-322. https://doi.org/10.3892/ijmm.2015.2224
Copy and paste a formatted citation
x
Spandidos Publications style
Li L, Wang X, Wang L, Qu L, Zhu X, Li M, Dang X, Li P, Gao Y, Peng Z, Peng Z, et al: Mammalian target of rapamycin overexpression antagonizes chronic hypoxia-triggered pulmonary arterial hypertension via the autophagic pathway. Int J Mol Med 36: 316-322, 2015.
APA
Li, L., Wang, X., Wang, L., Qu, L., Zhu, X., Li, M. ... Wan, L. (2015). Mammalian target of rapamycin overexpression antagonizes chronic hypoxia-triggered pulmonary arterial hypertension via the autophagic pathway. International Journal of Molecular Medicine, 36, 316-322. https://doi.org/10.3892/ijmm.2015.2224
MLA
Li, L., Wang, X., Wang, L., Qu, L., Zhu, X., Li, M., Dang, X., Li, P., Gao, Y., Peng, Z., Pan, L., Wan, L."Mammalian target of rapamycin overexpression antagonizes chronic hypoxia-triggered pulmonary arterial hypertension via the autophagic pathway". International Journal of Molecular Medicine 36.1 (2015): 316-322.
Chicago
Li, L., Wang, X., Wang, L., Qu, L., Zhu, X., Li, M., Dang, X., Li, P., Gao, Y., Peng, Z., Pan, L., Wan, L."Mammalian target of rapamycin overexpression antagonizes chronic hypoxia-triggered pulmonary arterial hypertension via the autophagic pathway". International Journal of Molecular Medicine 36, no. 1 (2015): 316-322. https://doi.org/10.3892/ijmm.2015.2224
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