Molecular basis of restenosis and novel issues of drug-eluting stents

Abstract

Restenosis after stent deployment is an overreaction of the wound healing response after vascular injury, and is characterized by the sequence of inflammation, granulation, extracellular matrix remodeling, and smooth muscle cell (SMC) proliferation and migration. In contrast, reendothelialization of at least part of the injured vessel surface, which is essential in the wound healing process, may occur at the site of stenting. Recent advances in drug-eluting stents (DES) have substantially reduced restenosis, but do not contribute to improve long-term prognosis, compared with bare metal stents (BMS). One of the reasons may be that reendothelialization is impaired after DES stenting. Regenerated endothelial cells and proliferated SMCs in the neointima are both in part derived from their progenitor cells, which are mobilized from bone marrow to injured vessel sites and differentiate into both vascular endothelial cells and SMCs. DES inhibits mobilization and differentiation of endothelial and smooth muscle progenitor cells, and thus not only inhibits restenosis but also impairs reendothelialization, which may lead to late stent thrombosis. To improve long-term prognosis in the DES era, adjunctive medical treatments inducing early reendothelialization, but inhibiting SMC proliferation, would be required.