The effects of vinblastine on smooth muscle cells in vitro: evaluation of a therapeutic window for the treatment of restenosis.
The development of drug-eluting stents (DES) to combat the problem of in-stent restenosis has revolutionized interventional cardiology. However, concerns have emerged about the risk of late angiographic stent thromboses associated with DES. The evaluation and width of the therapeutic window of a particular DES system is of huge importance to its safety and efficacy. In this study, the effects of vinblastine, an antimitotic drug, on smooth muscle cells in vitro is analyzed. The change in levels of proliferation, activity, migration, and viability in human coronary artery smooth muscle cells was measured at a range of concentrations and over a number of time points. These findings were then compared with those of a previous study on the effects of vinblastine on endothelial cells, and an optimum working concentration range was evaluated. This study suggests that the concentration of vinblastine most appropriate in restenosis treatment would be between 0.1 and 1 nM. At this concentration, vinblastine exerts a distinct effect on smooth muscle cell proliferation without detrimental effects on endothelial cell viability. It was also found that vinblastine affects certain cellular activities such as migration in a threshold-independent manner, suggesting that very low doses could be active against the processes of restenosis.
Gallagher
Hilary
H
National Centre for Biomedical Engineering Science, Galway, Ireland. hil.gallagher@gmail.com
Carroll
William M
WM
Rochev
Yuri
Y
D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000188:drug therapy*; D003331:Coronary Vessels / Q000166:cytology; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D054855:Drug-Eluting Stents; D006801:Humans; D008660:Metabolism / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014747:Vinblastine / Q000494:pharmacology*
D014747:Vinblastine; D004247:DNA; D020169:Caspases