Migration of smooth muscle and endothelial cells. Critical events in restenosis.

R estenosis after percutaneous transluminal coronary angioplasty (PTCA) continues to present a challenge.Multiple therapies, including an- tiplatelet and anticoagulant agents, calcium antagonists and inhibitors of angiotensin converting enzyme, corti- costeroids, endovascular prostheses, atherectomy, fish oil diets, and many other treatments have had only modest effects on the incidence of restenosis.12These results highlight how little we know of the underlying mechanisms. Pathology of RestenosisMost reports indicate that early restenosis -hours to days after PTCA-is due to thrombosis, with some contribution by elastic recoil and vasospasm.3,4In con- trast, the histology of late restenosis5-8 is mainly fibro- cellular proliferation with an extracellular matrix rang- ing from loose collagen fibrils and proteoglycans to dense collagen scar, with few inflammatory cells and little lipid in most cases.Fresh thrombus represents a minor component in the majority of specimens, but unlysed clot that has undergone hyaline change or been colonized by smooth muscle cells and macrophages is probably an important constituent in many cases.By light microscopy, most of the cells have a mesenchymal appearance, similar to that of fibroblasts.Electron microscopy reveals a variety of phenotypes.Some have substantial myofilament bundles and a basement mem- brane suggesting a smooth muscle cell (SMC) origin.This is supported by the presence of immunoreactivity for a,-smooth muscle actin and for vimentin and not desmin.5'7Other cells lack these features and may represent a more dedifferentiated SMC phenotype sim- ilar to the proliferating, migrating, matrix-secreting, neointimal cells in the balloon-injured rat, described below.9,'0This histological picture differs from that of stable atherosclerotic lesions.