International Journal of Gerontology
Volume 2, Issue 4 , Pages 158-166, December 2008

Beyond Oncogenesis: The Role of S-Phase Kinase-Associated Protein-2 (SKP2) In Vascular Restenosis

  • Yih-Jer Wu

      Affiliations

    • Cardiovascular Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    • Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr Yih-Jer Wu, Cardiovascular Medicine, Mackay Memorial Hospital, 92, Section 2, Chung Shan North Road, Taipei 10449, Taiwan
    • ,
  • Hung-I Yeh

      Affiliations

    • Cardiovascular Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    • Mackay Medicine, Nursing and Management College and Taipei Medical University, Taipei, Taiwan
    • ,
  • Charles Jia-Yin Hou

      Affiliations

    • Cardiovascular Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    • ,
  • Cheng-Ho Tsai

      Affiliations

    • Cardiovascular Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    • Mackay Medicine, Nursing and Management College and Taipei Medical University, Taipei, Taiwan
    • ,
  • Andrew C. Newby

      Affiliations

    • Bristol Heart Institute, University of Bristol, Bristol, United Kingdom
    • ,
  • Mark Bond

      Affiliations

    • Bristol Heart Institute, University of Bristol, Bristol, United Kingdom

Accepted 20 September 2008.

Article Outline

SUMMARY 

The clinical benefits of percutaneous coronary intervention, the most prevalent procedure nowadays for the treatment of symptomatic coronary artery disease, are frequently offset by the occurrence of vascular restenosis. Although the introduction of drug-eluting stents has significantly reduced restenotic rates, the rare, but potentially fatal, delayed thrombosis remains a clinical threat. Further refinement of the drug-eluting stent based on a better understanding of cell cycle regulation between the vascular smooth muscle cell (VSMC) and endothelial cell (EC) is required. In this review, we discuss the role of S-phase kinase-associated protein-2 (Skp2), previously known as an oncoprotein, in the regulation of VSMC proliferation and its signaling axis. The currently available evidence suggests that the Rac1-Skp2-p27Kip1 signaling axis acts as a common final pathway for many factors that regulate VSMC proliferation, such as growth factors, extracellular matrices and cyclic nucleotides. Importantly, although EC proliferation is also shown to be regulated by the same axis, cAMP seems to regulate this axis differentially between VSMC and EC, rendering the underlying mechanism of this differential regulation a promising target for the development of a new generation of drug-eluting stent.

Key Words:  coronary restenosis , cyclin-dependent kinase inhibitor p27 , myocytes , rac1 GTP-binding protein , smooth muscle , S-phase kinase-associated proteins

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PII: S1873-9598(09)70004-3

doi:10.1016/S1873-9598(09)70004-3

International Journal of Gerontology
Volume 2, Issue 4 , Pages 158-166, December 2008

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