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Differential profile of the OPG/RANKL/RANK-system in degenerative aortic native and bioprosthetic valves

Martin Steinmetz1, Dirk Skowasch, Nicolas Wernert

  • 1Department of Internal Medicine II, Division of Cardiology, University of Bonn, Germany. Martin.Steinmetz@ukb.uni-bonn.de

The Journal of Heart Valve Disease
|June 3, 2008
PubMed

Insights

The OPG/RANKL/RANK system is involved in native aortic valve calcification, but not bioprosthetic degeneration. This suggests new therapeutic targets for aortic stenosis.

Area of Science:

  • Cardiovascular Biology
  • Bone Metabolism
  • Immunology

Background:

  • Degenerative calcific aortic valve stenosis is common in the elderly.
  • The etiology of aortic stenosis and bioprosthetic degeneration is not fully understood.
  • The OPG/RANKL/RANK system regulates bone and immune metabolism.

Purpose of the Study:

  • To assess the expression of OPG/RANKL/RANK system determinants in calcific aortic valve stenosis.
  • To investigate the role of these determinants in porcine aortic bioprostheses degeneration.

Main Methods:

  • Valve tissue from 69 patients (aortic stenosis, sclerosis, bioprostheses) was analyzed.
  • Immunostaining and morphometry were used to detect OPG, RANKL, RANK, and NF-kappaB.
  • Expression levels and localization were quantified.

Main Results:

  • OPG, RANKL, RANK, and NF-kappaB were detected in stenotic and sclerotic valves.
  • Bioprostheses showed sparse signaling for these markers.
  • Sclerotic valves had increased OPG, RANK, and NF-kappaB, but decreased RANKL compared to stenotic valves, resulting in a lower OPG/RANKL ratio.

Conclusions:

  • The OPG/RANKL/RANK axis is implicated in native aortic valve calcification.
  • This system does not appear to play a significant role in porcine bioprosthetic degeneration.
  • These mediators may offer novel therapeutic targets for aortic stenosis.
Abstract

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