Endocrine Abstracts (2013) 32 P201 | DOI: 10.1530/endoabs.32.P201

Changes of expression of regulators of calcification in different stages of atherosclerosis in vasculature and bone

Natascha Schweighofer1, Ariane Aigelsreiter2, Martina Graf-Rechberger2, Nicole Hacker1, Martin Schweiger1, Olivia Trummer1, Thomas Pieber1, Matthias Ulbing1, Helmut Müller1 & Barbara Obermayer-Pietsch1

1Department of Internal Medicine, Divison of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria; 2Institute of Pathology, Medical University of Graz, Graz, Austria.

Calcification is physiologically present in bone but also pathophysiologically in the vasculature, favouring cardiovascular diseases. Our aim was to investigate changes in the expression of calcification regulators (CR) during vascular calcification in bone and vasculature. Gene expression levels of OPG, RANKL, OPN, MGP, BSP-II and RUNX2 were determined in bone, aorta and arteria ilica externa tissue samples of 22 transplant donors. Gene expression levels during atherosclerotic changes in the vessels were investigated using three histological stages of atherosclerosis (0) no changes, (1) intima thickening or (2) intima calcification. Patients’ other tissue samples were subgrouped accordingly. In addition, serum measurements of PTH, Fetuin A, 25(OH)Vitamin-D3 and 1,25(OH)2-Vitamin-D3 were performed.

Results: The comparison of gene expression of CR in vascular tissue revealed that the expression of CR was already changed in thickened vessels and kept stable during calcification. Therefore, we compared unaffected with affected vessels. We demonstrated that the expression of BSP-II and OPN were significantly (P=0.034) and RANKL expression was by trend decreased (P=0.085) in affected vessels compared to unaffected ones. In comparing bone and vascular tissue, patients with no atherosclerosis (stage 0) showed no differences in CR expression in bone and vascular tissue. In stage 1 patients, expression of MGP (P=0.002) and OPG (P=0.001) was significantly higher in bone than in both vessel types, whereas in stage 2 patients, OPG expression increased in both vessel types. Serum levels of Fetuin A were significantly lower in stage 2 patients compared to the other stages (P=0.007).

Conclusion: Our study indicates that changes in the expression of CR in the vessel wall as well as in bone tissue occurs already in the stage of thickening of the vessel wall, even prior to deposition of calcium/phosphate precipitation.