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Thromb Haemost 2007; 97(06): 1003-1012
DOI: 10.1160/TH06-10-0586
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Comparative characterization of cellular and molecular anti-restenotic profiles of paclitaxel and sirolimus

Implications for local drug delivery
Rainer Wessely
1   Deutsches Herzzentrum, Department of Cardiology / 1. Medizinische Klinik rechts der Isar, University of Technology, Munich, Germany
,
Birgit Blaich
1   Deutsches Herzzentrum, Department of Cardiology / 1. Medizinische Klinik rechts der Isar, University of Technology, Munich, Germany
,
Rachida Siham BelAiba
2   Deutsches Herzzentrum, Department of Pediatric Cardiology, University of Technology, Munich, Germany
,
Sabine Merl
1   Deutsches Herzzentrum, Department of Cardiology / 1. Medizinische Klinik rechts der Isar, University of Technology, Munich, Germany
,
Agnes Görlach
2   Deutsches Herzzentrum, Department of Pediatric Cardiology, University of Technology, Munich, Germany
,
Adnan Kastrati
1   Deutsches Herzzentrum, Department of Cardiology / 1. Medizinische Klinik rechts der Isar, University of Technology, Munich, Germany
,
Albert Schömig
1   Deutsches Herzzentrum, Department of Cardiology / 1. Medizinische Klinik rechts der Isar, University of Technology, Munich, Germany
› Author Affiliations
Further Information

Publication History

Received 15 October 2006

Accepted after resubmission 30 March 2007

Publication Date:
27 November 2017 (online)

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Summary

Pleiotropic anti-restenotic properties of drugs that are eluted from coated stents are critical for efficacy and safety. Little is known about comparative drug properties in appropriate human coronary target cell lines for the two compounds that are utilized on FDA-approved drug-eluting stent (DES) platforms, paclitaxel (PTX) and sirolimus (SRL). Target cell lines that play a pivotal role for the pathogenesis of restenosis and vascular healing include human coronary artery smooth muscle (CASMC) and endothelial cells (CAEC). PTX and SRL inhibited CASMC and CAEC proliferation and migration efficiently. However, there was a differential effect on proliferation and migration in CAEC with a more profound inhibition of both parameters by PTX, even at low dosages. Induction of cytotoxicity and apoptosis was pronounced in PTX- and very modest in SRL-treated CASMC and CAEC. PTX increased eNOS activity and nitric oxide (NO) release from CAEC. Neutrophilic leukocyte activation and transmigration, which should be avoided since it may precipitate adverse coronary events such as restenosis and stent thrombosis, was suppressed by SRL, whereas PTX tended to increase neutrophilic leucocyte activity. Therefore, although the primary drug target, inhibition of mitogen-mediated CASMC proliferation, is effectively accomplished by both drugs, auxiliary pharmacological properties that are crucial for the anti-restenotic drug effect and vascular healing are considerably different between PTX and SRL. In comparison with PTX, SRL shows minor interference with endothelial cell proliferation and migration, lower levels of cytotoxicity and apoptosis, a broader therapeutic range and distinctive immunosuppressive properties.

Keywords

endothelium - Drug-eluting stent - paclitaxel - sirolimus - smooth muscle cell
 

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