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International Journal of Molecular Medicine
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October 2014 Volume 34 Issue 4

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Article

siRNA-mediated silencing of Wnt5a regulates inflammatory responses in atherosclerosis through the MAPK/NF-κB pathways

  • Authors:
    • Lei Yang
    • Yingjie Chu
    • Yuhang Wang
    • Xiangmei Zhao
    • Wenke Xu
    • Peirong Zhang
    • Xiaoyu Liu
    • Shujuan Dong
    • Wenqi He
    • Chuanyu Gao
  • View Affiliations / Copyright

    Affiliations: Department of Emergency Medicine, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China, Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China
  • Pages: 1147-1152
    |
    Published online on: July 22, 2014
       https://doi.org/10.3892/ijmm.2014.1860
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Abstract

Previous studies have demonstrated that the aberrant expression of Wnt5a occurs in atherosclerotic lesions. However, the precise role of Wnt5a in the pathogenesis of atherosclerosis remains largely unknown. The present study was undertaken to determine whether the RNA interference of Wnt5a in vivo by adenovirus (Ad)-mediated small interfering RNA (siRNA) transfection is capable of inhibiting the progression of atherosclerosis. Recombinant adenovirus carrying siRNA targeting Wnt5a (Ad-Wnt5a siRNA) was designed. Male apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat diet to induce the pathogenesis of atherosclerosis. Mice were randomly divided into 3 groups (n=15 in each group): the mock group, which received treatment with phosphate-buffered saline (PBS); the Ad-NC group, which received treatment with Ad-non-specific siRNA; and the Ad-Wnt5a siRNA group, which received treatment with Ad-Wnt5a siRNA. Treatment with Ad-Wnt5a siRNA markedly inhibited the mRNA and protein expression of Wnt5a in the aortic tissues. The knockdown of Wnt5a had no significant effect on blood lipid levels, but it suppressed atherosclerotic development and increased plaque stability, which was determined by hematoxylin and eosin staining, picrosirius red staining and Oil Red O staining. Furthermore, the mRNA and protein expression of inflammatory cytokines, including monocyte chemotactic protein-1 (MCP-1), cyclooxygenase-2 (COX-2), matrix metalloproteinase (MMP)-2 and MMP-9 was significantly downregulated in the Ad-Wnt5a siRNA group. In addition, the knockdown of Wnt5a inhibited the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. These results demonstrate that Ad-mediated Wnt5a silencing in vivo attenuates the development of atherosclerotic disease by reducing inflammatory mediators involved in the MAPK/NF-κB pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Yang L, Chu Y, Wang Y, Zhao X, Xu W, Zhang P, Liu X, Dong S, He W, Gao C, Gao C, et al: siRNA-mediated silencing of Wnt5a regulates inflammatory responses in atherosclerosis through the MAPK/NF-κB pathways. Int J Mol Med 34: 1147-1152, 2014.
APA
Yang, L., Chu, Y., Wang, Y., Zhao, X., Xu, W., Zhang, P. ... Gao, C. (2014). siRNA-mediated silencing of Wnt5a regulates inflammatory responses in atherosclerosis through the MAPK/NF-κB pathways. International Journal of Molecular Medicine, 34, 1147-1152. https://doi.org/10.3892/ijmm.2014.1860
MLA
Yang, L., Chu, Y., Wang, Y., Zhao, X., Xu, W., Zhang, P., Liu, X., Dong, S., He, W., Gao, C."siRNA-mediated silencing of Wnt5a regulates inflammatory responses in atherosclerosis through the MAPK/NF-κB pathways". International Journal of Molecular Medicine 34.4 (2014): 1147-1152.
Chicago
Yang, L., Chu, Y., Wang, Y., Zhao, X., Xu, W., Zhang, P., Liu, X., Dong, S., He, W., Gao, C."siRNA-mediated silencing of Wnt5a regulates inflammatory responses in atherosclerosis through the MAPK/NF-κB pathways". International Journal of Molecular Medicine 34, no. 4 (2014): 1147-1152. https://doi.org/10.3892/ijmm.2014.1860
Copy and paste a formatted citation
x
Spandidos Publications style
Yang L, Chu Y, Wang Y, Zhao X, Xu W, Zhang P, Liu X, Dong S, He W, Gao C, Gao C, et al: siRNA-mediated silencing of Wnt5a regulates inflammatory responses in atherosclerosis through the MAPK/NF-κB pathways. Int J Mol Med 34: 1147-1152, 2014.
APA
Yang, L., Chu, Y., Wang, Y., Zhao, X., Xu, W., Zhang, P. ... Gao, C. (2014). siRNA-mediated silencing of Wnt5a regulates inflammatory responses in atherosclerosis through the MAPK/NF-κB pathways. International Journal of Molecular Medicine, 34, 1147-1152. https://doi.org/10.3892/ijmm.2014.1860
MLA
Yang, L., Chu, Y., Wang, Y., Zhao, X., Xu, W., Zhang, P., Liu, X., Dong, S., He, W., Gao, C."siRNA-mediated silencing of Wnt5a regulates inflammatory responses in atherosclerosis through the MAPK/NF-κB pathways". International Journal of Molecular Medicine 34.4 (2014): 1147-1152.
Chicago
Yang, L., Chu, Y., Wang, Y., Zhao, X., Xu, W., Zhang, P., Liu, X., Dong, S., He, W., Gao, C."siRNA-mediated silencing of Wnt5a regulates inflammatory responses in atherosclerosis through the MAPK/NF-κB pathways". International Journal of Molecular Medicine 34, no. 4 (2014): 1147-1152. https://doi.org/10.3892/ijmm.2014.1860
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