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- Title
Neointimal Expression of Rapamycin Receptor FK506-Binding Protein FKBP12: Postinjury Animal and Human In-Stent Restenosis Tissue Characteristics.
- Authors
Bauriedel, Gerhard; Jabs, Alexander; Kraemer, Stefan; Nickenig, Georg; Skowasch, Dirk
- 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
- Subjects
DENDRITIC cells; SURGICAL stents; CORONARY restenosis; RAPAMYCIN; ARTERIAL catheterization
- Publication
Journal of Vascular Research, 2008, Vol 45, Issue 2, p173
- ISSN
1018-1172
- Publication type
Article
- DOI
10.1159/000110417