Drug-eluting stents: Sirolimus and paclitaxel differentially affect cultured cells and injured arteries

Tom J. Parry, Ruth Brosius, Rathna Thyagarajan, Demetrius Carter, Dennis Argentieri, Robert Falotico, John Siekierka

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Sirolimus and paclitaxel eluted from stents inhibit cell proliferation and other cellular processes by dramatically different mechanisms. In this study, the effects of sirolimus and paclitaxel on cultured human coronary artery smooth muscle and endothelial cell function or cell cycle changes in balloon-injured arteries were directly compared. Both sirolimus and paclitaxel inhibited smooth muscle and endothelial cell proliferation. However, only paclitaxel inhibited smooth muscle and endothelial cell migration at low (nM) concentrations. Sirolimus arrested smooth muscle and endothelial cells in the G0/G1 phase of the cell cycle without inducing apoptosis while paclitaxel produced apoptosis in both cell types at low nanomolar concentrations. Although both agents blocked neointimal formation, sirolimus applied locally to injured rat carotid arteries increased the percentage of cycling vascular cells in G0/G1 without inducing apoptosis while paclitaxel increased the percentage of cycling cells in S and G2/M phases while inducing apoptosis. These results suggest that sirolimus reduces neointimal hyperplasia through a cytostatic mechanism while paclitaxel produces apoptotic cell death.

Original languageEnglish
Pages (from-to)19-29
Number of pages11
JournalEuropean Journal of Pharmacology
Volume524
Issue number1-3
DOIs
StatePublished - 7 Nov 2005

Keywords

  • Cell cycle
  • Cell proliferation
  • Paclitaxel
  • Restenosis
  • Sirolimus

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