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European Heart Journal Advance Access published online on August 22, 2005

European Heart Journal, doi:10.1093/eurheartj/ehi458
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European Heart Journal © The European Society of Cardiology 2005; all rights reserved
Received March 29, 2005
Revised July 20, 2005
Accepted July 22, 2005

Clinical research

Cells of primarily extravalvular origin in degenerative aortic valves and bioprostheses

Dirk Skowasch 1*, Stephanie Schrempf 1, Nicolas Wernert 2, Martin Steinmetz 1, Alexander Jabs 1, Izabela Tuleta 1, Ulrich Welsch 3, Claus J. Preusse 4, James A. Likungu 4, Armin Welz 4, Berndt Lüderitz 1, and Gerhard Bauriedel 1

1 Department of Cardiology, Heart Center University of Bonn, Bonn, Germany
2 Institute of Pathology, University of Bonn, Bonn, Germany
3 Institute of Anatomy II, University of Munich, Munich, Germany
4 Department of Heart Surgery, Heart Center University of Bonn, Bonn, Germany

* To whom correspondence should be addressed.
Dirk Skowasch, E-mail: dirk.skowasch{at}ukb.uni-bonn.de


   Abstract

Aims We assessed aortic valves from patients with non-rheumatic aortic valve stenosis (AS) and with degenerative aortic valve bioprostheses (BP) for the presence of progenitor cell and leukocyte subtype-specific markers.

Methods and results Diseased valve probes from a total of 87 patients (60 AS and 27 BP) were studied. We assessed presence and localization of endothelial progenitor cells (EPCs: CD34, CD133), dendritic cells (DCs: S100), T-lymphocytes (CD3), and macrophages (CD68) by immunohistochemical and morphometric analyses. In the majority of valves, we detected cell-bound signals of CD34 (48% of AS, 74% of BP, respectively), CD133 (58%/81%), S100 (58%/93%), CD3 (62%/81%), and CD68 (78%/93%). Labelled cells were predominantly localized within the valvular fibrosa. As key results, frequency of EPCs, DCs, macrophages, and lymphocytes was found significantly higher in BP when compared with AS (CD34: 19.2 ± 23.2 vs. 5.7 ± 13.0%; CD133: 13.7 ± 12.4 vs. 5.5 ± 8.3%; S100: 15.2 ± 12.2 vs. 5.7 ± 8.9%; CD3: 3.3 ± 2.7 vs. 1.1 ± 1.4%; CD68: 35.3 ± 26.6 vs. 3.4 ± 4.1%; each P ≤ 0.001).

Conclusion EPCs and DCs were detected in a large collective of degenerative aortic valves, more frequently in bioprostheses than in native cusps. Aortoluminal presence of these primarily extravalvular cells co-localized with inflammatory cells is a novel key feature involved in aortic valve degeneration.

Keywords: Aortic valve prostheses; Degenerative aortic stenosis; Dendritic cells; Endothelial progenitor cells; Inflammation.
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