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Digoxin inhibits PDGF-BB-induced VSMC proliferation and migration through an increase in ILK signaling and attenuates neointima formation following carotid injury

  • Authors:
    • Gaoliang Yan
    • Qingjie Wang
    • Shengda Hu
    • Dong Wang
    • Yong Qiao
    • Genshan Ma
    • Chengchun Tang
    • Yuchun Gu
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Zhongda Hospital of Southeast University Medical School, Nanjing, Jiangsu 210009, P.R. China, Institute of Molecular Medicine (IMM), Peking University, Beijing 100190, P.R. China
    Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1001-1011
    |
    Published online on: August 21, 2015
       https://doi.org/10.3892/ijmm.2015.2320
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Abstract

The increased proliferation and migration of vascular smooth muscle cells (VSMCs) are key events in the development of artery restenosis following percutaneous coronary intervention. Digoxin has long been used in the treatment of heart failure and has been shown to inhibit the proliferation of cancer cells through multiple pathways. However, the potential role of digoxin in the regulation of VSMC proliferation and migration and its effectiveness in the treatment of cardiovascular diseases, such as restenosis, remains unexplored. In the present study, we demonstrate that digoxin-induced growth inhibition is associated with the downregulation of CDK activation and the restoration of p27Kip1 levels in platelet-derived growth factor (PDGF)-stimulated VSMCs. In addition, we found that digoxin restored the PDGF‑BB-induced inhibition of integrin linked kinase (ILK) expression and prevented the PDGF‑BB-induced activation of glycogen synthase kinase (GSK)-3β. Furthermore, digoxin inhibited adhesion molecule and extracellular matrix relative protein expression. Finally, we found that digoxin significantly inhibited neointima formation, accompanied by a decrease in cell proliferation following vascular injury in rats. These effects of digoxin were shown to be mediated, at least in part, through an increase in ILK/Akt signaling and a decrease in GSK-3β signaling in PDGF‑BB-stimulated VSMCs. In conclusion, our data demonstrate that digoxin exerts an inhibitory effect on the PDGF‑BB-induced proliferation, migration and phenotypic modulation of VSMCs, and prevents neointima formation in rats. These observations indicate the potential therapeutic application of digoxin in the treatment of cardiovascular diseases, such as restenosis.
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Copy and paste a formatted citation
Spandidos Publications style
Yan G, Wang Q, Hu S, Wang D, Qiao Y, Ma G, Tang C and Gu Y: Digoxin inhibits PDGF-BB-induced VSMC proliferation and migration through an increase in ILK signaling and attenuates neointima formation following carotid injury. Int J Mol Med 36: 1001-1011, 2015.
APA
Yan, G., Wang, Q., Hu, S., Wang, D., Qiao, Y., Ma, G. ... Gu, Y. (2015). Digoxin inhibits PDGF-BB-induced VSMC proliferation and migration through an increase in ILK signaling and attenuates neointima formation following carotid injury. International Journal of Molecular Medicine, 36, 1001-1011. https://doi.org/10.3892/ijmm.2015.2320
MLA
Yan, G., Wang, Q., Hu, S., Wang, D., Qiao, Y., Ma, G., Tang, C., Gu, Y."Digoxin inhibits PDGF-BB-induced VSMC proliferation and migration through an increase in ILK signaling and attenuates neointima formation following carotid injury". International Journal of Molecular Medicine 36.4 (2015): 1001-1011.
Chicago
Yan, G., Wang, Q., Hu, S., Wang, D., Qiao, Y., Ma, G., Tang, C., Gu, Y."Digoxin inhibits PDGF-BB-induced VSMC proliferation and migration through an increase in ILK signaling and attenuates neointima formation following carotid injury". International Journal of Molecular Medicine 36, no. 4 (2015): 1001-1011. https://doi.org/10.3892/ijmm.2015.2320
Copy and paste a formatted citation
x
Spandidos Publications style
Yan G, Wang Q, Hu S, Wang D, Qiao Y, Ma G, Tang C and Gu Y: Digoxin inhibits PDGF-BB-induced VSMC proliferation and migration through an increase in ILK signaling and attenuates neointima formation following carotid injury. Int J Mol Med 36: 1001-1011, 2015.
APA
Yan, G., Wang, Q., Hu, S., Wang, D., Qiao, Y., Ma, G. ... Gu, Y. (2015). Digoxin inhibits PDGF-BB-induced VSMC proliferation and migration through an increase in ILK signaling and attenuates neointima formation following carotid injury. International Journal of Molecular Medicine, 36, 1001-1011. https://doi.org/10.3892/ijmm.2015.2320
MLA
Yan, G., Wang, Q., Hu, S., Wang, D., Qiao, Y., Ma, G., Tang, C., Gu, Y."Digoxin inhibits PDGF-BB-induced VSMC proliferation and migration through an increase in ILK signaling and attenuates neointima formation following carotid injury". International Journal of Molecular Medicine 36.4 (2015): 1001-1011.
Chicago
Yan, G., Wang, Q., Hu, S., Wang, D., Qiao, Y., Ma, G., Tang, C., Gu, Y."Digoxin inhibits PDGF-BB-induced VSMC proliferation and migration through an increase in ILK signaling and attenuates neointima formation following carotid injury". International Journal of Molecular Medicine 36, no. 4 (2015): 1001-1011. https://doi.org/10.3892/ijmm.2015.2320
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