COLCHICINE ANTAGONIZES THE ACTIVITY OF HUMAN SMOOTH-MUSCLE CELLS CULTIVATED FROM ARTERIOSCLEROTIC LESIONS AFTER ATHERECTOMY

Aim: Proliferative, migratory, and secretory activities of vascular sm ooth muscle cells are functional determinants of human atherosclerotic plaque and restenosis formation. The present study was designed to ex amine the effects of interfering with these processes using drugs. Mat erials and methods: For in-vitro studies of smooth muscle cell activit y, arterial smooth muscle cells were cultivated from human plaque tiss ue excised from 22 coronary and peripheral lesions and treated with th e antitubulin colchicine. Smooth muscle cell migratory activity was an alyzed by a standardized semi-automatic video system. Transmission ele ctron microscopy was used to examine cytoplasmic structures. Results: Colchicine caused a concentration-dependent decrease in smooth muscle cell proliferative activity at a half-maximal inhibitory concentration (IC50) Of 5 nmol/l. Smooth muscle cell migratory activity was reduced by colchicine in a concentration-dependent manner (IC50, 3 nmol/l). C oncordantly, transmission electron microscopy revealed severe disorgan ization of cytoplasmic structures, especially of organelles, indicatin g metabolic activation. Conclusions: In-vitro studies with human smoot h muscle cells from arteriosclerotic lesions suggest that the antitubu lin principle may be useful in producing anti-arteriosclerotic effects , since a pronounced antagonization of smooth muscle cell proliferativ e, migratory, and secretory processes, indirectly inferred from ultras tructural analysis, was demonstrated with low concentrations of colchi cine.