Abstract 19375: Platelet Activation Plays an Important Role in Regulation of Aortic Valve Calcification in Calcific Aortic Valve Disease
Background: The most significant predictor of valve disease progression is the load of calcium in aortic valve. Dickkopf-1 (DKK-1) might be along the causal pathway in regulation of valvular calcification. The effects of DKK-1 are mediated by inhibition of Wnt signaling, which directly limited osteoprotegerin (OPG) expression. It was suggested, that a significant amount of DKK-1 is produced by activated platelets.
Purpose: The study focused on serum levels, aortic valve tissue concentrations and mRNA expression of DKK-1 and OPG.
Methods: Serum DKK-1 and OPG were measured in patients with symptomatic CAS (N=313) and control group without CAS (N=100). Tissue samples were collected during AVR (N=172) and from explanted hearts during transplantation (N=116).
Results: Serum DKK-1 and OPG were significantly higher in CAS in comparison to control group; DKK [Median (5th; 95th percentile): 1.5 (0.3; 3.8) vs. 1.0 (0.2; 3.4) ng/ml; p=0.002] and OPG [7.5 (3.5; 16.0) vs. 4.6 (2.6; 10.4) pmol/l; p<0.001]. Concentrations of DKK were significantly higher in tissue from CAS [131.5 (11.2; 889.7) pg/ml] in comparison with normal valves [27.3 (5.2; 764.2) pg/ml; p<0.001]. Results for OPG were analogical; OPG in CAS [17.9 (3.4; 122.3) pmol/l] and normal valves [5.3 (1.0;48.5) pmol/l; p<0.001]. mRNA expression of hTNFESF11B (OPG) was significantly lower in tissue from stenotic valves [1.16 (1.11;1.22)] in comparison to expression in tissue from normal valves [1.21 (1.14;1.42); p<0.001]. DKK1 protein expression was not detected in valve tissue.
In CAS, significant correlations were found between a) circulating and tissue DKK-1 (rs=-0.573;p=0.003), b) circulating DKK-1 and tissue OPG (rs = -0.410;p=0.047). Circulating and tissue DKK-1 also correlated with circulating levels of platelet derived RANTES (rs=0.449;p=0.024) and Platelet factor 4 (rs=0.697;p<0.0001).
Conclusion: Circulating platelet-derived DKK-1 is significantly higher in CAS in comparison to normal aortic valves. Significant negative correlation was observed between serum DKK-1 and tissue concentration of OPG. mRNA expression of OPG was significantly lower in stenotic valves in comparison to normal aortic valve.
Author Disclosures: Z. Motovska: None. R. Fojt: None. J. Jarkovsky: None. Z. Straka: None. P. Widimsky: None. J. Pirk: None.
- © 2016 by American Heart Association, Inc.