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

  • Published online on: June 6, 2017     https://doi.org/10.3892/mmr.2017.6706
  • Pages: 1360-1368
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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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August-2017
Volume 16 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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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