A PRESCREENING SYSTEM FOR POTENTIAL ANTIPROLIFERATIVE AGENTS - IMPLICATIONS FOR LOCAL TREATMENT STRATEGIES OF POSTANGIOPLASTY RESTENOSIS

Background, Recent advances in the understanding of the biology of res tenosis indicate that it is predominantly caused by a multifactorial s timulation of smooth muscle cell proliferation. The aim of this study was to investigate the in vitro effect of five potential antiprolifera tive agents on smooth muscle cells from human atherosclerotic femoral arteries, Methods and results, Primary stenosing plaque material of 24 patients (aged 63 +/- 14 years) and restenosing plaque material of 7 patients (aged 65 +/- 9 years) was selectively extracted from femoral arteries by the Simpson atherectomy device. Cells were isolated by enz ymatic disaggregation and identified as smooth muscle cells by positiv e reaction with smooth muscle cu-actin. Dalteparin sodium (0.001-100 a nti-Xa units/ml), cyclosporine A (0.005-500 mu g/ml), colchicine (0.00 004-4 pg/ml), etoposide (0.002-200 mu g/ml), and doxorubicin (0.0005-5 0 mu g/ml) were added to the cultures, Six days after seeding, cells w ere trypsinized and cell number was measured by a cell counter. All fi ve agents tested exhibited a significant inhibition of smooth muscle c ell proliferation (P < 0.001). After an incubation time of 48 h, the c ytoskeletal components, alpha-actin, vimentin, and microtubules were i nvestigated. At peak concentrations, all five tested agents except dal teparin sodium caused severe damage to the cytoskeleton. Conclusions. All five potential antiproliferative agents exhibited a significant in hibition of smooth muscle cell proliferation. The development of new i ntravascular delivery systems may open the way for local antiprolifera tive treatment strategies in interventional cardiology.