ECTS2016 Poster Presentations Other diseases of bone and mineral metabolism (52 abstracts)
Calcification in the vessel wall: impact of vitamin K dependent proteins
Natascha Schweighofer 1 , Ariane Aigelsreiter 2 , Olivia Trummer 1 , Daniela Kniepeiss 3 , Doris Wagner 3 , Philipp Stiegler 3 , Thomas Pieber 1, , Helmut Müller 3 & Barbara Obermayer-Pietsch 1,
1Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria; 2Institute of Pathology, Medical University of Graz, Graz, Austria; 3Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, Graz, Austria; 4CBmed, Center for Biomarker Research in Medicine, Graz, Austria.
Pathophysiological calcification in the vasculature favours cardio- and cerebrovascular diseases. In patients with chronic kidney disease vitamin K metabolites are associated with decreased vascular calcification.
We investigated the expression of vitamin K dependent proteins (VKDPs) in vessels and bone to identify differences in expression pattern during atherosclerosis (AS) stages and compare the two tissue profiles.
Gene expression levels of BSP, MGP, OC, TGFBI, GRP, GAS6, periostin, PRRG1-4, protein Z and S were examined with predesigned TaqMan assays on a LC480 system in vessels (external iliac artery and aorta) and bone of 26 organ donors. Relative Cp values were obtained by division with beta actin.
Determination of calcification stages was done histologically: no changes: unaffected vessels, intima thickening: more than one-fold intima thickening without calcification, intima calcification: one or more calcification spots.
Gene expression of MGP, TGFBI, GAS6, periostin, protein S and PRRG1 decreased in bone compared to vessels in atherosclerosis (P=0.001, P<0.001, P<0.001, P<0.001, P=0.001, and P=0.001).
In vessels gene expression of GRP, PRRG1, 3 and 4 were decreased in atherosclerosis compared to normal state (P=0.037, P=0.002, P=0.011, P=0.011). In bone gene expression of BSP decreased when atherosclerotic vessels were present (P=0.018).
Looking at three stages of atherosclerosis, differences in gene expression of TGFBI (P=0.023) and periostin (P=0.002) are seen in intima thickening, in intima calcification also MGP (P=0.007), GAS6 (P<0.001), protein S (P=0.002) and PRRG1 (P=0.001) show differences in gene expression in bone and vessels.
In vessels PRRG1 (P=0.013), 3 (P=0.048) and 4 (P=0.049) gene expression decreased during intima thickening and keeps low in the calcification stage. In bone gene expression of VKDPs did not change during AS progression.
Gene expression of vitamin K dependent proteins changes during calcification of the vessel wall, implicating a more complex role of vitamin K dependent proteins in vascular calcification than previously known.
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