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; pu003c0.001]. Concentratio...