title: Experimental assessment of effects of antiproliferative drugs of drug-eluting stents on endothelial cells.
abstract: BACKGROUND
  Late and very late stent thrombosis after drug-eluting stent implantation is a major concern. The present study evaluated difference in the effects of sirolimus, paclitaxel and zotarolimus on endothelial cells.
  
  
  METHODS
  Mouse endothelial cells were seeded in a 6-well plate. Cells were cultured with an antiproliferative drug at the expected concentrations for each well for 24 hours before making 3 scratch lines with a pipette tip. After a 4.5 hour incubation period, 3 reference scratch lines, vertically across the original scratch lines, were made in the same way. The experiment was repeated at least 6 times (6 plates). Measurements were performed at 9 crossings of each well. Wound healing ratio was calculated as 1-(distance of the first scratch/distance of the second scratch). % cell migration was calculated as (wound healing ratio at an expected drug concentration/wound healing ratio with no drug) × 100. Average % cell migration at 54 crossings of 6 plates was calculated.
  
  
  RESULTS
  Paclitaxel inhibited cell migration in a concentration-dependent manner. On the other hand, concentration-dependent inhibition was not observed for sirolimus or zotarolimus. Sirolimus showed a stronger inhibitory effect on migration of endothelial cells compared to zotarolimus.
  
  
  CONCLUSIONS
  The difference in the effect of antiproliferative drugs of drug-eluting stents on endothelial cells may be associated with relatively faster re-endothelialization of zotarolimus-eluting stent compared to the 1st generation DES.
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. Electronic address: markone@hospital.chiba-u.jp.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Miura
authors.affiliation: Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Haruaki
authors.initials: H
authors.lastname: Nakaya
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000187:drug effects*; D051379:Mice; D017239:Paclitaxel / Q000494:pharmacology*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C489443:zotarolimus; D017239:Paclitaxel; D020123:Sirolimus
keywords: Drug-eluting stent; Paclitaxel; Sirolimus; Zotarolimus