Implication of bone regulatory factors in human coronary artery calcification

Abstract

Background: Although emerging evidence suggests that vascular calcification constitutes an active process sharing common features with bone formation, several aspects of this process in human coronary artery calcification are still poorly understood. We therefore investigated the expression of key bone regulatory factors in human atherosclerotic coronary arteries. Methods – Results: Formalin, fixed-paraffin embedded tissue samples of human atherosclerotic coronary arteries (n = 41) and normal arteries as controls (n = 9) were studied immunohistochemically for the expression of osteoprotegerin (OPG), RANKL, RANK, Runx2, Sox9, NFATc1 and Osterix (Osx). All factors where expressed in atherosclerotic lesions while absent in normal arteries, with the exception of OPG. While expression of NFATc1 and Osx was confined to tunica intima of diseased arteries, the others factors were expressed in both tunica intima and tunica media. Most factors were expressed in smooth muscle-like cells of tunica intima while NFATc1 and the OPG/RANKL/RANK system were also expressed in inflammatory cells. Wheareas expression of OPG and RANKL was invariable, expression of RANK, Runx2, Sox9, Osx and NFATc1 was significantly higher in advanced calcified lesions. Significant correlations were also observed among the bone regulatory factors in atherosclerotic arteries. Conclusions: Our results confirm the hypothesis that highly regulated osteogenic processes are involved in the mineralization of human coronary arteries and implicate the bone regulatory factors Osx and NFATc1 in coronary artery calcification.

Keywords

• Bone
• Coronary
• Artery
• Calcification