Differential profile of the OPG/RANKL/RANK-system in degenerative aortic native and bioprosthetic valves.
OBJECTIVE
Although degenerative calcific aortic valve stenosis is the most common valvular disease among the elderly, neither the etiology underlying the condition nor degeneration of the bioprostheses is yet fully understood. The study aim was to assess the expression profile of those OPG/RANKL/RANK-system determinants known to act as key regulators of bone metabolism and the immune system in calcific aortic valve stenosis and porcine aortic bioprostheses.


METHODS
Valve probes from a total of 69 patients (41 with end-stage aortic stenosis, 11 with mild-to-moderate aortic sclerosis, 17 with degenerative porcine aortic bioprostheses) were explanted either during surgery or at autopsy. The presence and localization of OPG, RANKL, RANK and NF-kappaB were analyzed by immunostaining and morphometry.


RESULTS
The majority of stenotic and sclerotic valves exhibited cell-bound signals of OPG, RANKL, RANK and NF-kappaB, while bioprostheses showed only sparse signaling. As key findings, the percentage of cells labeled by OPG, RANK and NF-kappaB was increased in sclerotic valves compared with stenotic valves (each p < 0.001), whereas the frequency of RANKL was higher in stenotic compared to sclerotic valves (p < 0.001). As a consequence, the OPG/RANKL ratio was decreased in stenotic (0.83) compared to sclerotic valves (20.2).


CONCLUSIONS
The differential expression profile of specific members of the OPG/RANKL/RANK axis suggests an involvement of their determinants in native valve calcification, but not in the degeneration of porcine bioprostheses. Thus, these mediators of bone homeostasis may represent new targets for a more specified prevention and/or therapy of native aortic stenosis.
Steinmetz
Martin
M
Department of Internal Medicine II, Division of Cardiology, University of Bonn, Germany. Martin.Steinmetz@ukb.uni-bonn.de
Skowasch
Dirk
D
Wernert
Nicolas
N
Welsch
Ulrich
U
Preusse
Clauss J
CJ
Welz
Armin
A
Nickenig
Georg
G
Bauriedel
Gerhard
G
D000368:Aged; D001024:Aortic Valve Stenosis / Q000378:metabolism* / Q000473:pathology; D001705:Bioprosthesis; D002114:Calcinosis / Q000378:metabolism; D005260:Female; D006350:Heart Valve Prosthesis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D012189:Retrospective Studies
D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B