The role of osteoprotegerin system/RANKL/rank in pathogenesis of aortic stenosis

Abstract

Aim. To assess the concentrations of osteoprotegerin (OPG) and soluble ligand of the receptor of transcription activator factor kappa-B (sRANKL) in the blood serum of patients with various grade of aortic stenosis (AS) severity. Material and methods. Totally, 247 AS patients studied of various grade: 46 — mild, 53 — moderate and 149 — severe. Of those 132 (53%) with bicuspid aortic valve (BAV) and 115 (47%) with tricuspid (TAV). Controls were 58 patients with no valvular pathology or coronary heart disease. All patients underwent lipid profile measurement, serum C-reactive protein (CRP) and OPG, sRANKL. Results. In all studied groups of AS patients there was increased level of sRANKL in blood serum, comparing to controls (BAV =0,37 [0,32;0,53] pM/L, TAV =0,38 [0,33;0,50] pM/L, controls 0,30 [0,21;0,39] pM/L; р<0,0001). Concentration of OPG was increased only in TAV: 6,99 [5,19;9,90] pM/L; comparing to 5,23 [4,30;7,09] pM/L in BAV (р=0,0008). A hypothesis proposed that OPG concentration increase is compensatory and takes place as a response to the increase of the concentration or due to loss of sensitivity to sRANKL. Conclusion. Development of AS is related to disorders in OPG/RANKL system, and these revealed changes might have significant diagnostic and predictive value, especially in TAV.