Bone regulatory factors NFATc1 and Osterix in human calcific aortic valves

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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.