Bench to bedside: the development of rapamycin and its application to stent restenosis. Circulation

In response to physiological stimuli (eg, wound healing),normally quiescent smooth muscle cells (SMCs) withinthe vessel wall can be activated to migrate and proliferate to produce new blood vessels. In addition to this physiolog-ical response, pathological migration and proliferation within the vessel wall can occur in disease states. Examples of such disease states include tumor growth and metastasis, diabetic retinopathy, arthritis, accelerated arteriopathy after cardiac transplantation, and neointimal proliferation after balloon angioplasty (PTCA) and stent placement. An important lim-itation of PTCA is restenosis, which is due in large part to luminal narrowing; restenosis occurs in 20 % to 40 % of patients within the first few months after a successful inter-vention.1,2 The percentage of patients that develop early restenosis after PTCA can be reduced by stent implantation. However, stents actually increase the amount of late luminal narrowing due to intimal hyperplasia,3 and the overall rate o