Colchicine antagonizes the activity of human smooth muscle cells cultivated from arteriosclerotic lesions after atherectomy.
OBJECTIVE
Proliferative, migratory, and secretory activities of vascular smooth muscle cells are functional determinants of human atherosclerotic plaque and restenosis formation. The present study was designed to examine the effects of interfering with these processes using drugs.


METHODS
For in-vitro studies of smooth muscle cell activity, arterial smooth muscle cells were cultivated from human plaque tissue excised from 22 coronary and peripheral lesions and treated with the antitubulin colchicine. Smooth muscle cell migratory activity was analyzed by a standardized semi-automatic video system. Transmission electron 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). Concordantly, transmission electron microscopy revealed severe disorganization of cytoplasmic structures, especially of organelles, indicating metabolic activation.


CONCLUSIONS
In-vitro studies with human smooth muscle cells from arteriosclerotic lesions suggest that the antitubulin principle may be useful in producing anti-arteriosclerotic effects, since a pronounced antagonization of smooth muscle cell proliferative, migratory, and secretory processes, indirectly inferred from ultrastructural analysis, was demonstrated with low concentrations of colchicine.
Bauriedel
G
G
Department of Internal Medicine I, Klinikum Grosshadern, Germany.
Heimerl
J
J
Beinert
T
T
Welsch
U
U
Höfling
B
B
D008841:Actin Cytoskeleton / Q000187:drug effects; D000199:Actins; D001161:Arteriosclerosis / Q000473:pathology* / Q000503:physiopathology; D017073:Atherectomy; D017225:Atherectomy, Coronary; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology*; D003324:Coronary Artery Disease / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D008870:Microtubules / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015388:Organelles / Q000187:drug effects; D014741:Video Recording
D000199:Actins; D003078:Colchicine