BEYOND ONCOGENESIS: THE ROLE OF S-PHASE KINASE-ASSOCIATED PROTEIN-2 (SKP2) IN VASCULAR RESTENOSIS

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-p27(Kip1) signaling axis acts as a common final pathway for many factors that regulate VSMC proliferation, such as growth factors, extracellular matrices and cyclic nucleoticles. 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. [International Journal of Gerontology 2008; 2(4): 158-166]