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Comparative Assessment of Transient Exposure of Paclitaxel or Zotarolimus on In Vitro Vascular Cell Death, Proliferation, Migration, and Proinflammatory Biomarker Expression

Steinfeld, Donald S. BS; Liu, Annie P. MS; Hsu, Steven H. PhD; Chan, Yen F.; Stankus, John J. PhD; Pacetti, Stephen D. MS; Tai, Julie T. PhD

Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0b013e31825aa742
Original Article
Abstract

Abstract: Both paclitaxel and zotarolimus are currently employed in vascular interventional therapies, such as drug-eluting stents, and are under investigation for use in other novel drug–device combination products. Paclitaxel is a microtubule-stabilizing compound with potent antiproliferative properties and antimigration effects, whereas zotarolimus is a potent mammalian target of rapamycin inhibitor with antiproliferative and antiinflammatory properties. This study was intended to compare paclitaxel and zotarolimus for intravascular applications in which drug exposure time may be reduced, such as in drug-coated balloons. These applications are generally aimed at reducing neointimal hyperplasia by limiting smooth muscle cell (SMC) proliferation and inflammatory cell recruitment, while minimally interfering with vessel reendothelialization after balloon denudation. In the cellular models described in this study, transient exposure of zotarolimus resulted in the sustained inhibition of SMC proliferation and reduced endothelial cell (EC) proinflammatory cytokine expression, while not affecting EC migration and viability. Transient exposure of paclitaxel inhibited SMC proliferation, EC migration, and overall cell viability, with no effect on expression of the proinflammatory biomarkers studied.

Author Information

Abbott Vascular, Santa Clara, CA

Reprints: Steven H. Hsu, PhD, Abbott Vascular, M/S 232, 3200 Lakeside Drive, Santa Clara, CA 95054-2087 (e-mail: steven.hsu@av.abbott.com).

Supported by Abbott Vascular.

All the authors are full-time employees of Abbott Vascular (a division of Abbott Laboratories).

Received April 6, 2011

Accepted April 16, 2012

© 2012 Lippincott Williams & Wilkins, Inc.