The effects of vinblastine on endothelial cells.
The development of drug-eluting stents 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 drug-eluting stents. It has been shown that noncytotoxic concentrations of paclitaxel exert an antiangiogenic effect, suggesting that paclitaxel and similar agents may inhibit key cellular functions in a threshold-independent manner. In this study, the effect of vinblastine, an antimitotic drug, on endothelial cells is analyzed. It is investigated whether noncytotoxic concentrations of the drug could exert an antirestenotic effect. The change in levels of cell proliferation, activity, and viability in human umbilical vein endothelial cells was measured at a range of concentrations and over a number of time points. Also, the level of apoptotic activity in response to vinblastine was analyzed. This study shows 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 biological effect without causing an increase in apoptotic activity. These results emphasize the importance of finding an appropriate concentration window in order to minimize the risk of delayed endothelialization and thrombosis.
National Centre for Biomedical Engineering Science and Department of Chemistry, National University of Ireland, Galway, Galway, Ireland.
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Gallagher
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Carroll
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Dowd
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Rochev
D050256:Antimitotic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology; D001560:Benzidines / Q000378:metabolism; D006690:Bisbenzimidazole / Q000378:metabolism; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002863:Chromogenic Compounds / Q000378:metabolism; D023903:Coronary Restenosis / Q000517:prevention & control; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D054855:Drug-Eluting Stents / Q000009:adverse effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents / Q000032:analysis / Q000378:metabolism; D010078:Oxazines / Q000032:analysis / Q000378:metabolism; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D014747:Vinblastine / Q000494:pharmacology*; D014966:Xanthenes / Q000032:analysis / Q000378:metabolism
D050256:Antimitotic Agents; D001560:Benzidines; D002863:Chromogenic Compounds; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D010078:Oxazines; D014966:Xanthenes; C005843:resazurin; C021758:3,3',5,5'-tetramethylbenzidine; D014747:Vinblastine; D004247:DNA; D053148:Caspase 3; D006690:Bisbenzimidazole