Bone regulatory factors NFATc1 and Osterix in human calcific aortic valves

Alexopoulos, Alexandros; Bravou, Vasiliki; Peroukides, Stavros; Kaklamanis, Loukas; Varakis, John; Alexopoulos, Dimitrios; Papadaki, Helen

doi:10.1016/j.ijcard.2008.10.014

« Previous Next »International Journal of Cardiology
Volume 139, Issue 2 , Pages 142-149, 4 March 2010

Bone regulatory factors NFATc1 and Osterix in human calcific aortic valves☆

Alexandros Alexopoulos
- Department of Anatomy, School of Medicine, University of Patras, Greece
Vasiliki Bravou
- Department of Anatomy, School of Medicine, University of Patras, Greece
Stavros Peroukides
- Department of Anatomy, School of Medicine, University of Patras, Greece
Loukas Kaklamanis
- Department of Pathology, Onassis Cardiac Surgery Center, Athens, Greece
John Varakis
- Department of Anatomy, School of Medicine, University of Patras, Greece
Dimitrios Alexopoulos
- Department of Cardiology, University Hospital of Patras, Greece
Helen Papadaki
- Department of Anatomy, School of Medicine, University of Patras, Greece
- Corresponding author. Department of Anatomy, School of Medicine, University of Patras, 26500 Rio, Patras, Greece. Tel.: +30 2610992391; fax: +30 2610997886.

Received 20 April 2008; received in revised form 26 August 2008; accepted 12 October 2008. published online 19 November 2008.

Abstract

Background

Emerging evidence suggests that calcific aortic valve stenosis constitutes an active process sharing common features with atherosclerosis and bone formation. To further support this hypothesis, we investigated the expression of bone regulatory factors in calcified aortic valves.

Methods–results

Formalin-fixed, paraffin-embedded tissue samples of human aortic tricuspid valves (n=54) were used from patients undergoing valve replacement for calcific, non-rheumatic aortic stenosis. As controls, fourteen aortic tricuspid valves (n=14) were obtained at autopsy from patients without clinical and morphological aortic valve lesions. Sections from both stenotic and normal aortic valve leaflets were studied immunohistochemically. Interstitial cells in stenotic valves showed intense expression of Sox9, Runx2 and Osterix (Osx) whereas NFATc1 was expressed in interstitial and inflammatory cells. In addition, NFATc1 expression correlated significantly with Osx (r=0.458, p<0.001) and Runx2 (r=0.387, p<0.001). Finally, there was accumulation of activated interstitial cells, T lymphocytes and macrophages as well as intense neoangiogenesis in pathological leaflets.

Conclusions

The presence of NFATc1 and Osx in our material lends further support to the hypothesis that during the process of aortic valve calcification there is expression of osteoblastic phenotypes by valvular cells.

Keywords: Calcific, Aortic valves, NFATc1, Osterix