Publication Date
2011
Journal
The Texas Heart Journal
PMID
21423464
Publication Date(s)
2011
Language
English
PMCID
PMC3060757
PubMedCentral® Posted Date
2011
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
Drug-eluting stents/adverse effects, endothelial cells, immunosuppressive agents/administration & dosage, paclitaxel/therapeutic use, thrombin, thrombomodulin, thrombosis/etiology
Copyright
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Abstract
Patients with paclitaxel-eluting stents are at risk of developing stent thrombosis upon premature discontinuation of dual antiplatelet therapy. In this study, we set out to clarify whether paclitaxel can modulate thrombomodulin expression in human aortic endothelial cells. Human aortic endothelial cells were stimulated with paclitaxel. Methoxyphenyl tetrazolium inner salt cell viability assay, Western blot analysis, real-time polymerase chain reaction, and immunohistochemical assay were performed. In human aortic endothelial cells, paclitaxel (10(-5) to 10(-9) mol/L) treatment for 13 hours caused significant cytotoxicity at drug concentrations greater than 10(-7) mol/L. Paclitaxel (10(-5) to 10(-9) mol/L) treatment for 5 hours downregulated thrombomodulin expression dose-dependently, persisting even at 13 hours. Cotreatment with thrombin and paclitaxel did not alter the effect of paclitaxel on thrombomodulin downregulation. Paclitaxel caused a 0.63-fold decrease in thrombomodulin messenger RNA expression, and thrombin cotreatment did not alter this decrease. In vivo studies confirmed that paclitaxel (10 mg/kg) caused endothelial thrombomodulin downregulation in mice. In summary, paclitaxel downregulates thrombomodulin expression regardless of thrombin stimulation, which is an important factor for patients receiving paclitaxel-eluting stents. Therefore, further designs of drug-eluting stents should consider the influence of the eluted drugs on endothelial thrombogenicity.