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Article

4-Chloro-DL-phenylalanine protects against monocrotaline‑induced pulmonary vascular remodeling and lung inflammation

  • Authors:
    • Yang Bai
    • Han-Ming Wang
    • Ming Liu
    • Yun Wang
    • Guo-Chao Lian
    • Xin-Hua Zhang
    • Jian Kang
    • Huai-Liang Wang
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Pharmacology, School of Pharmacy, China Medical University, Shenyang, P.R. China, National Key Subject, Institute of Respiratory Diseases, China Medical University, Shenyang, P.R. China
  • Pages: 373-382
    |
    Published online on: December 16, 2013
       https://doi.org/10.3892/ijmm.2013.1591
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Abstract

The present study was performed to investigate the effects of 4-chloro-DL-phenylalanine (PCPA), a tryptophan hydroxylase (Tph) inhibitor (TphI), on pulmonary vascular remodeling and lung inflammation in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. Animal models of PAH were established using Sprague-Dawley (SD) rats by a single intraperitoneal injection of MCT (60 mg/kg). PCPA (50 or 100 mg/kg/day) was administered to the rats with PAH. On day 22, hemodynamic measurements and morphological observations of the lung tissues were performed. The levels of Tph-1 and serotonin transporter (SERT) in the lungs were analyzed by immunohistochemistry and western blot analysis. The expression of matrix metalloproteinase (MMP)-2 and MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 and inflammatory cytokines were assayed by western blot analysis. The activity of MMP-2 and MMP-9 was evaluated by gelatin zymography (GZ). MCT markedly promoted PAH, increased the right ventricular hypertrophy index, pulmonary vascular remodeling, lung inflammation and mortality, which was associated with the increased expression of Tph-1, SERT, MMP-2/-9, TIMP-1/-2 and inflammatory cytokines. PCPA markedly attenuated MCT-induced pulmonary vascular remodeling and lung inflammation, inhibited the expression of Tph-1 and SERT and suppressed the expression of MMP-2/-9, TIMP-1/-2, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1). These findings suggest that the amelioration of MCT-induced pulmonary vascular remodeling and lung inflammation by PCPA is associated with the downregulation of Tph-1, SERT, MMP/TIMP and inflammatory cytokine expression in rats.
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Copy and paste a formatted citation
Spandidos Publications style
Bai Y, Wang H, Liu M, Wang Y, Lian G, Zhang X, Kang J and Wang H: 4-Chloro-DL-phenylalanine protects against monocrotaline‑induced pulmonary vascular remodeling and lung inflammation. Int J Mol Med 33: 373-382, 2014.
APA
Bai, Y., Wang, H., Liu, M., Wang, Y., Lian, G., Zhang, X. ... Wang, H. (2014). 4-Chloro-DL-phenylalanine protects against monocrotaline‑induced pulmonary vascular remodeling and lung inflammation. International Journal of Molecular Medicine, 33, 373-382. https://doi.org/10.3892/ijmm.2013.1591
MLA
Bai, Y., Wang, H., Liu, M., Wang, Y., Lian, G., Zhang, X., Kang, J., Wang, H."4-Chloro-DL-phenylalanine protects against monocrotaline‑induced pulmonary vascular remodeling and lung inflammation". International Journal of Molecular Medicine 33.2 (2014): 373-382.
Chicago
Bai, Y., Wang, H., Liu, M., Wang, Y., Lian, G., Zhang, X., Kang, J., Wang, H."4-Chloro-DL-phenylalanine protects against monocrotaline‑induced pulmonary vascular remodeling and lung inflammation". International Journal of Molecular Medicine 33, no. 2 (2014): 373-382. https://doi.org/10.3892/ijmm.2013.1591
Copy and paste a formatted citation
x
Spandidos Publications style
Bai Y, Wang H, Liu M, Wang Y, Lian G, Zhang X, Kang J and Wang H: 4-Chloro-DL-phenylalanine protects against monocrotaline‑induced pulmonary vascular remodeling and lung inflammation. Int J Mol Med 33: 373-382, 2014.
APA
Bai, Y., Wang, H., Liu, M., Wang, Y., Lian, G., Zhang, X. ... Wang, H. (2014). 4-Chloro-DL-phenylalanine protects against monocrotaline‑induced pulmonary vascular remodeling and lung inflammation. International Journal of Molecular Medicine, 33, 373-382. https://doi.org/10.3892/ijmm.2013.1591
MLA
Bai, Y., Wang, H., Liu, M., Wang, Y., Lian, G., Zhang, X., Kang, J., Wang, H."4-Chloro-DL-phenylalanine protects against monocrotaline‑induced pulmonary vascular remodeling and lung inflammation". International Journal of Molecular Medicine 33.2 (2014): 373-382.
Chicago
Bai, Y., Wang, H., Liu, M., Wang, Y., Lian, G., Zhang, X., Kang, J., Wang, H."4-Chloro-DL-phenylalanine protects against monocrotaline‑induced pulmonary vascular remodeling and lung inflammation". International Journal of Molecular Medicine 33, no. 2 (2014): 373-382. https://doi.org/10.3892/ijmm.2013.1591
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