The in-vitro effect of antineoplastic agents on proliferative activity and cytoskeletal components of plaque-derived smooth-muscle cells from human coronary arteries.
BACKGROUND
Restenosis after successful percutaneous transluminal coronary angioplasty remains the major clinical problem limiting the long-term efficacy of the treatment. Recent advances in the understanding of the biology of restenosis indicate that its cause is predominantly a multifactorial stimulation of smooth-muscle cell proliferation. The aim of this study was to investigate the in-vitro effect of antineoplastic agents on smooth-muscle cells isolated from human coronary plaque material.


METHODS
Atherosclerotic tissue from coronary arteries was extracted from 15 patients of both sexes by thrombendarterectomy. Cells were isolated using enzymatic disaggregation and identified to be smooth-muscle cells with fluorescent antibodies for smooth-muscle-specific alpha-actin. The antineoplastic agents cytarabine (500-0.005 micrograms/ml), doxorubicin (50-0.0005 micrograms/ml), and vincristine (10-0.0001 micrograms/ml) were added to the cultures. Six days after seeding, the cells were trypsinized and then counted.


RESULTS
All three antineoplastic agents had a strong dose-dependent antiproliferative effect on cultured smooth-muscle cells. After the application of cytostatic agents, cells either became rounded or underwent complete lysis. Cytoskeletal elements, such as actin, microtubules, and vimentin, were largely altered.


CONCLUSIONS
This investigation examined the potential role of antineoplastic therapy in the prevention of restenosis after coronary angioplasty. The development of new intravascular delivery systems, such as coated stents, may open the way for local antiproliferative strategies in interventional cardiology.
Voisard
R
R
Department of Cardiology, Angiology, Nephrology and Pneumology, University of Ulm, Germany.
Dartsch
P C
PC
Seitzer
U
U
Hannekum
A
A
Roth
D
D
Kochs
M
M
Hombach
V
V
D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000473:pathology* / Q000628:therapy; D003561:Cytarabine / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000032:analysis; D003599:Cytoskeleton / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D012008:Recurrence; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D003598:Cytoskeletal Proteins; D003561:Cytarabine; D014750:Vincristine; D004317:Doxorubicin