[Growth-inhibiting effect of colchicine on cultured vascular wall myocytes from arteriosclerotic lesions].

Abstract

Proliferative, migratory, and secretory activities of vascular smooth muscle cells are currently discussed as determinants of human plaque and restenosis formation. Affecting these determinants with drugs may promise anti-arteriosclerotic effects. Plaque tissue was removed from both coronary and peripheral lesions of a total of 18 patients to cultivate smooth muscle cells (SMC) for subsequent in vitro studies. The antitubulin colchicine (C) caused a concentration-dependent decrease of SMC proliferative activity with an IC50 of 5 x 10(-9) M. Migratory activity was analyzed by a standardized semi-automatic video system. This parameter was reduced by C in a concentration-dependent manner (IC50: 5 x 10(-10) M). As shown by immunofluorescence microscopy, the typical structure of microtubules of C-treated SMCs was distorted, whereas the pattern of alpha-actin filaments remained unaltered. Transmission electron microscopy (TEM) revealed that the number of microtubules was diminished after addition of C, and that a distinct disorganization of cytoplasmic organelles as well as the formation of vacuoles had occurred. In vitro studies of human smooth muscle cells derived from vascular plaques indicate that colchicine may be useful as an anti-arteriosclerotic drug, since a concentration-dependent concordant effect on proliferation, migration, and secretory processes of the SMC could be demonstrated.