Expression of bone-related proteins in vascular calcification and its serum correlations with coronary artery calcification score

Abstract

Since vascular calcification is considered a process regulated similar to that of bone tissue mineralization, we investigated the participation of bone formation proteins. We analyzed the correlation of serum circulating bone markers, osteoprotegerin (OPG) and receptor activator of nuclear factor ĸB ligand (RANKL) in chronic kidney disease (CKD) patients, to coronary artery calcification score. We also considered the effect of inorganic phosphate on pro- and anti-calcifying tissue factors. We confirmed that circulating OPG is an independent calcium score predictor with its high serum concentration favoring high coronary artery calcification. In tissue samples of non-diseased human renal arteries, the expression of OPG and receptor activator of nuclear factor ĸB (RANK) was positive, while expression of RANKL was absent. In atherosclerotic specimens and arteries with medial calcification, the most upregulated was expression of bone morphogenetic proteins, BMP-2 and BMP-7, as well as expression of RANK and RANKL. In the diseased arteries, OPG expression was present only in areas where bone structures were formed. In atherosclerotic and medial calcification arteries, loss of alpha-smooth muscle actin (α-SMA) expression was observed. These data suggest a possible regulatory role of the examined proteins, especially OPG and RANKL, in vascular calcification, as well as their possible clinical significance as circulating predictors of vascular calcification.