PLATELET ACTIVATION PLAYS AN IMPORTANT ROLE IN REGULATION OF AORTIC VALVE CALCIFICATION IN CALCIFIC AORTIC VALVE DISEASE

Background. Dickkopf-1 (DKK-1) might be along the causal pathway in regulation of valvular calcification. 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 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]. In CAS, significant correlations were found between a) circulating and tissue DKK-1, b)circulating DKK-1 and tissue OPG. Circulating and tissue DKK-1 also correlated with circulating levels of platelet derived RANTES and Platelet factor 4.

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.