Research Paper

Neointimal Expression of Rapamycin Receptor FK506-Binding Protein FKBP12: Postinjury Animal and Human In-Stent Restenosis Tissue Characteristics
Gerhard Bauriedel^{a, b}, Alexander Jabs^a, Stefan Kraemer^a, Georg Nickenig^a, Dirk Skowasch<sup>a

a</sup>Department of Internal Medicine II - Cardiology, University of Bonn, Bonn, and
^bDepartment of Internal Medicine I - Cardiology, Klinikum Meiningen, Meiningen, Germany

Address of Corresponding Author

J Vasc Res 2008;45:173-178 (DOI: 10.1159/000110417)

  Key Words

• Dendritic cells
• Drug-eluting stents
• In-stent restenosis
• Rapamycin

  Abstract

Despite excellent clinical results for sirolimus (rapamycin)-eluting stents, the exact mechanisms of antirestenotic activity and affected cellular targets are incompletely understood. Therefore, we determined the presence and tem- porospatial expression pattern of FKBP12, the primary intracellular receptor of rapamycin, in rat carotid arteries after balloon injury, as well as in human in-stent restenosis and primary stable coronary atheroma. FKBP12 expression was assessed by immunohistochemistry. Rat carotid arteries revealed maximal expression in 57.7 ± 4.0% of neointimal cells at day 7. A large proportion of these FKBP12+ cells showed luminally confined co-expression with dendritic cell markers. Despite a considerably thicker neointima at day 28, presence of FKBP12 decreased (8.5 ± 1.9%, p = 0.02) with a scattered pattern in luminal and deep neointima. Likewise, human in-stent restenosis atherectomy specimens (time after stent implantation 2-12 months) revealed a comparable extent of cellular rapamycin receptor expression (9.3 ± 1.0%) that significantly differed from that found in primary stable atheroma (1.3 ± 0.4%, p < 0.001). In conclusion, the rapamycin receptor is predominantly present during early neointima formation, while mature neointimal atheromas show a relatively low expression without confinement to luminal areas. Co-expression of FKBP12 and dendritic cell markers suggests that dendritic cells may be another important target for early and long-term rapamycin effects.

Copyright © 2007 S. Karger AG, Basel

  Author Contacts

Prof. Dr. med. Gerhard Bauriedel
Department of Internal Medicine I - Cardiology, Klinikum Meiningen
Bergstrasse 3, DE-98617 Meiningen (Germany)
Tel. +49 3693 901 475, Fax +49 3693 181 043
E-Mail g.bauriedel.med1@klinikum-meiningen.de

  Article Information

Received: January 11, 2007
Accepted after revision: August 8, 2007
Published online: October 26, 2007
Number of Print Pages : 6
Number of Figures : 2, Number of Tables : 1, Number of References : 24