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Article

EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells

  • Authors:
    • Wenjing Feng
    • Xizhen Xu
    • Gang Zhao
    • Geng Li
    • Tiantian Liu
    • Junjie Zhao
    • Ruolan Dong
    • Dao Wen Wang
    • Ling Tu
  • View Affiliations / Copyright

    Affiliations: Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China
  • Pages: 685-693
    |
    Published online on: July 5, 2013
       https://doi.org/10.3892/ijmm.2013.1435
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Abstract

Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) have multiple biological functions in cardiovascular homeostasis. The anti-inflammatory, anti-migratory and pro-proliferative effects of EETs suggest a possible beneficial role for EETs in the apoptosis, proliferation and migration of pulmonary vascular cells. In this study, we investigated the effects of exogenous EETs and cytochrome P450 2J2 (CYP2J2) overexpression on tumor necrosis factor-α (TNF-α)-induced pulmonary artery endothelial cell (PAEC) apoptosis, and transforming growth factor-β1 (TGF-β1)-induced pulmonary artery smooth muscle cell (PASMC) proliferation and migration. PAECs and PASMCs were cultured from porcine pulmonary arteries. Our findings indicated that EETs or CYP2J2 overexpression significantly protected the PAECs from TNF-α-induced apoptosis, as evaluated by cell viability and flow cytometry. Two mechanisms were found to be involved in these important protective effects: firstly, EETs and CYP2J2 overexpression inhibited the decrease in the expression of the antiapoptotic proteins, Bcl-2 and Bcl-xL, as well as the increase in the expression of the pro-apoptotic protein, Bax, mediated by TNF-α; secondly, they activated the phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling pathways. We also found that 11,12-EET and 14,15-EET significantly inhibited TGF-β1-stimulated PASMC migration. However, EETs did not suppress TGF-β1-induced PASMC proliferation in vitro. These data may represent a novel approach to mitigate pulmonary vascular remodeling in diseases, such as pulmonary arterial hypertension.
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Copy and paste a formatted citation
Spandidos Publications style
Feng W, Xu X, Zhao G, Li G, Liu T, Zhao J, Dong R, Wang DW and Tu L: EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells. Int J Mol Med 32: 685-693, 2013.
APA
Feng, W., Xu, X., Zhao, G., Li, G., Liu, T., Zhao, J. ... Tu, L. (2013). EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells. International Journal of Molecular Medicine, 32, 685-693. https://doi.org/10.3892/ijmm.2013.1435
MLA
Feng, W., Xu, X., Zhao, G., Li, G., Liu, T., Zhao, J., Dong, R., Wang, D. W., Tu, L."EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells". International Journal of Molecular Medicine 32.3 (2013): 685-693.
Chicago
Feng, W., Xu, X., Zhao, G., Li, G., Liu, T., Zhao, J., Dong, R., Wang, D. W., Tu, L."EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells". International Journal of Molecular Medicine 32, no. 3 (2013): 685-693. https://doi.org/10.3892/ijmm.2013.1435
Copy and paste a formatted citation
x
Spandidos Publications style
Feng W, Xu X, Zhao G, Li G, Liu T, Zhao J, Dong R, Wang DW and Tu L: EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells. Int J Mol Med 32: 685-693, 2013.
APA
Feng, W., Xu, X., Zhao, G., Li, G., Liu, T., Zhao, J. ... Tu, L. (2013). EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells. International Journal of Molecular Medicine, 32, 685-693. https://doi.org/10.3892/ijmm.2013.1435
MLA
Feng, W., Xu, X., Zhao, G., Li, G., Liu, T., Zhao, J., Dong, R., Wang, D. W., Tu, L."EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells". International Journal of Molecular Medicine 32.3 (2013): 685-693.
Chicago
Feng, W., Xu, X., Zhao, G., Li, G., Liu, T., Zhao, J., Dong, R., Wang, D. W., Tu, L."EETs and CYP2J2 inhibit TNF-α-induced apoptosis in pulmonary artery endothelial cells and TGF-β1-induced migration in pulmonary artery smooth muscle cells". International Journal of Molecular Medicine 32, no. 3 (2013): 685-693. https://doi.org/10.3892/ijmm.2013.1435
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