SERPINE1 Regulates Vascular Smooth Muscle Cell Survival: Attenuation of Neointimal Hyperplasia with a Small Molecule Functional Inhibitor That Promotes SERPINE1 Cleavage

Restenosis is a pathological form of wound healing following endovascular interventions that involves increased vascular smooth muscle cell (VSMC) migration/proliferation combined with reduced apoptosis resulting in luminal narrowing. The incidence of restenosis varies (range 20-50%) among the specific procedures used (e.g., stenting vs. balloon angioplasty) and the vessel site. Of the several factors implicated in the vascular response to injury, plasminogen activator inhibitor-1 (PAI-1; SERPINE1), a member of the serine protease inhibitor (SERPIN) superfamily and the major physiologic regulator of the plasmin-based pericellular proteolytic cascade, is perhaps the most prominent.