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Article

Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents

  • Authors:
    • Yuyan Lu
    • Haipeng Guo
    • Yuxi Sun
    • Xin Pan
    • Jia Dong
    • Di Gao
    • Wei Chen
    • Yawei Xu
    • Dachun Xu
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong 250000, P.R. China
  • Pages: 1360-1368
    |
    Published online on: June 6, 2017
       https://doi.org/10.3892/mmr.2017.6706
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Abstract

It has previously been demonstrated that the renin-angiotensin system is involved in the pathogenesis and development of pulmonary hypertension (PH). However, the efficacy of angiotensin II type I (AT1) receptor blockers in the treatment of PH is variable. The present study examined the effects of the AT1 receptor blocker valsartan on monocrotaline (MCT)‑induced PH in rats and chronic hypoxia‑induced PH in mice. The results demonstrated that valsartan markedly attenuated development of PH in rats and mice, as indicated by reduced right ventricular systolic pressure, diminished lung vascular remodeling and decreased right ventricular hypertrophy, compared with vehicle treated animals. Immunohistochemical analyses of proliferating cell nuclear antigen expression revealed that valsartan suppressed smooth muscle cell proliferation. Western blot analysis demonstrated that valsartan limited activation of p38, c‑Jun N‑terminal kinase 1/2 and extracellular signal‑regulated kinase 1/2 signaling pathways and significantly reduced MCT‑induced upregulation of pulmonary matrix metalloproteinases‑2 and ‑9, and transforming growth factor‑β1 expression. The results suggested that valsartan attenuates development of PH in rodents by reducing expression of extracellular matrix remodeling factors and limiting smooth muscle cell proliferation to decrease pathological vascular remodeling. Therefore, valsartan may be a valuable future therapeutic approach for the treatment of PH.
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Copy and paste a formatted citation
Spandidos Publications style
Lu Y, Guo H, Sun Y, Pan X, Dong J, Gao D, Chen W, Xu Y and Xu D: Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents. Mol Med Rep 16: 1360-1368, 2017.
APA
Lu, Y., Guo, H., Sun, Y., Pan, X., Dong, J., Gao, D. ... Xu, D. (2017). Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents. Molecular Medicine Reports, 16, 1360-1368. https://doi.org/10.3892/mmr.2017.6706
MLA
Lu, Y., Guo, H., Sun, Y., Pan, X., Dong, J., Gao, D., Chen, W., Xu, Y., Xu, D."Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents". Molecular Medicine Reports 16.2 (2017): 1360-1368.
Chicago
Lu, Y., Guo, H., Sun, Y., Pan, X., Dong, J., Gao, D., Chen, W., Xu, Y., Xu, D."Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents". Molecular Medicine Reports 16, no. 2 (2017): 1360-1368. https://doi.org/10.3892/mmr.2017.6706
Copy and paste a formatted citation
x
Spandidos Publications style
Lu Y, Guo H, Sun Y, Pan X, Dong J, Gao D, Chen W, Xu Y and Xu D: Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents. Mol Med Rep 16: 1360-1368, 2017.
APA
Lu, Y., Guo, H., Sun, Y., Pan, X., Dong, J., Gao, D. ... Xu, D. (2017). Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents. Molecular Medicine Reports, 16, 1360-1368. https://doi.org/10.3892/mmr.2017.6706
MLA
Lu, Y., Guo, H., Sun, Y., Pan, X., Dong, J., Gao, D., Chen, W., Xu, Y., Xu, D."Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents". Molecular Medicine Reports 16.2 (2017): 1360-1368.
Chicago
Lu, Y., Guo, H., Sun, Y., Pan, X., Dong, J., Gao, D., Chen, W., Xu, Y., Xu, D."Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents". Molecular Medicine Reports 16, no. 2 (2017): 1360-1368. https://doi.org/10.3892/mmr.2017.6706
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