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Article

The Rho/Rho-associated protein kinase inhibitor fasudil in the protection of endothelial cells against advanced glycation end products through the nuclear factor κB pathway

  • Authors:
    • Yuyan Lu
    • Hailing Li
    • Weixia Jian
    • Jianhui Zhuang
    • Ke Wang
    • Wenhui Peng
    • Yawei Xu
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China, Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China
  • Pages: 310-316
    |
    Published online on: May 20, 2013
       https://doi.org/10.3892/etm.2013.1125
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Abstract

Accumulating evidence has demonstrated that the Rho/Rho-associated protein kinase (Rho/ROCK) and nuclear factor κB (NF-κB) signaling pathways are involved in the pathogenesis of diabetic vascular injury. In this study, we investigated the beneficial effects of fasudil, a ROCK inhibitor, on vascular endothelial injury induced by advanced glycation end products (AGEs) in vitro. Human umbilical vein endothelial cells (HUVECs) were stimulated with AGEs and AGEs plus fasudil in various concentrations for different time periods. Monocyte‑endothelial cell adhesion, vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression, protein expression and activation of Rho/ROCK, activation of NF-κB and reactive oxygen species (ROS) production were evaluated. Fasudil suppressed AGE-induced monocyte-endothelial adhesion. Fasudil also reduced the mRNA and protein expression of VCAM-1 and MCP-1 in a concentration- and time-dependent manner. Moreover, increases in the protein levels of Rho/ROCK and ROCK activity mediated by AGEs were inhibited by the addition of fasudil. Additionally, fasudil attenuated AGE-induced NF-κB-dependent transcriptional activity and inhibition of NF-κB (IκB) phosphorylation. ROS production induced by AGEs was also reduced by fasudil in HUVECs. The results suggest that ROCK inhibition may protect the vascular endothelium against AGE-induced monocyte‑endothelial adhesion in vitro through the reduction of ROS generation and the downregulation of NF-κB signaling. Thus, ROCK inhibition may be a novel therapeutic approach for the treatment of vascular complications in diabetes.
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Copy and paste a formatted citation
Spandidos Publications style
Lu Y, Li H, Jian W, Zhuang J, Wang K, Peng W and Xu Y: The Rho/Rho-associated protein kinase inhibitor fasudil in the protection of endothelial cells against advanced glycation end products through the nuclear factor κB pathway. Exp Ther Med 6: 310-316, 2013.
APA
Lu, Y., Li, H., Jian, W., Zhuang, J., Wang, K., Peng, W., & Xu, Y. (2013). The Rho/Rho-associated protein kinase inhibitor fasudil in the protection of endothelial cells against advanced glycation end products through the nuclear factor κB pathway. Experimental and Therapeutic Medicine, 6, 310-316. https://doi.org/10.3892/etm.2013.1125
MLA
Lu, Y., Li, H., Jian, W., Zhuang, J., Wang, K., Peng, W., Xu, Y."The Rho/Rho-associated protein kinase inhibitor fasudil in the protection of endothelial cells against advanced glycation end products through the nuclear factor κB pathway". Experimental and Therapeutic Medicine 6.2 (2013): 310-316.
Chicago
Lu, Y., Li, H., Jian, W., Zhuang, J., Wang, K., Peng, W., Xu, Y."The Rho/Rho-associated protein kinase inhibitor fasudil in the protection of endothelial cells against advanced glycation end products through the nuclear factor κB pathway". Experimental and Therapeutic Medicine 6, no. 2 (2013): 310-316. https://doi.org/10.3892/etm.2013.1125
Copy and paste a formatted citation
x
Spandidos Publications style
Lu Y, Li H, Jian W, Zhuang J, Wang K, Peng W and Xu Y: The Rho/Rho-associated protein kinase inhibitor fasudil in the protection of endothelial cells against advanced glycation end products through the nuclear factor κB pathway. Exp Ther Med 6: 310-316, 2013.
APA
Lu, Y., Li, H., Jian, W., Zhuang, J., Wang, K., Peng, W., & Xu, Y. (2013). The Rho/Rho-associated protein kinase inhibitor fasudil in the protection of endothelial cells against advanced glycation end products through the nuclear factor κB pathway. Experimental and Therapeutic Medicine, 6, 310-316. https://doi.org/10.3892/etm.2013.1125
MLA
Lu, Y., Li, H., Jian, W., Zhuang, J., Wang, K., Peng, W., Xu, Y."The Rho/Rho-associated protein kinase inhibitor fasudil in the protection of endothelial cells against advanced glycation end products through the nuclear factor κB pathway". Experimental and Therapeutic Medicine 6.2 (2013): 310-316.
Chicago
Lu, Y., Li, H., Jian, W., Zhuang, J., Wang, K., Peng, W., Xu, Y."The Rho/Rho-associated protein kinase inhibitor fasudil in the protection of endothelial cells against advanced glycation end products through the nuclear factor κB pathway". Experimental and Therapeutic Medicine 6, no. 2 (2013): 310-316. https://doi.org/10.3892/etm.2013.1125
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