Enzymes of the vitamin K cycle and progression of calcification in the vessel wall

Natascha Schweighofer; Ariane Aigelsreiter; Olivia Trummer; Martina Graf-Rechberger; Nicole Hacker; Florian Iberer; Doris Wagner; Daniela Kniepeiss; Philipp Stiegler; Thomas Pieber; Helmut Muller; Barbara Obermayer-Pietsch

doi:10.1530/endoabs.37.EP554

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Endocrine Abstracts (2015) 37 EP554 | DOI: 10.1530/endoabs.37.EP554

ECE2015 Eposter Presentations Obesity and cardiovascular endocrinology (108 abstracts)

Enzymes of the vitamin K cycle and progression of calcification in the vessel wall

Natascha Schweighofer ¹ , Ariane Aigelsreiter ² , Olivia Trummer ¹ , Martina Graf-Rechberger ² , Nicole Hacker ¹ , Florian Iberer ³ , Doris Wagner ³ , Daniela Kniepeiss ³ , Philipp Stiegler ³ , Thomas Pieber ¹ , Helmut Müller ³ & Barbara Obermayer-Pietsch ¹

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¹Department of Internal Medicine, Divison 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.

Calcification is a physiological process in bone but occurs also pathologically in the vasculature, favouring cardio- and cerebrovascular diseases (CVD). Vitamin K metabolites, particularly K1 and MK-4, are associated with decreased vascular calcification especially in patients with chronic kidney disease. We investigated the expression of components of the vitamin K cycle (VKC) and the MK-4 synthesis (MKS) in aorta and bone of 26 brain dead organ donors in order to identify differences in the expression pattern during atherosclerosis (AS) stages in aortic vascular tissue and to compare these profiles in both tissue types. Gene expression was performed using TaqMan gene expression assays with a LC480 system. Determination of calcification stage was done histologically: (0 (unaffected vessels), 1 (intima thickening), 2 (intima calcification)). VKC enzymes VKOR, VKORL1, GGCX and the chaperone calu and the enzymes NQO1 and UBIAD1, necessary for MKS are both expressed in aortic and bone tissue. In the aorta, gene expression of VKOR, VKORL1, and calu differed significantly between the three atherosclerotic stages (P=0.040; P=0.023 and P=0.038, respectively), whereas the expression of GGCX showed borderline significance (P=0.060). In bone, gene expression of VKC and the MKS proteins did not differ in respective AS stages. Comparison of bone and aorta showed only significant differences in gene expression of calu, GGCX and NQO1 in the last stage of intima calcification. We are able to demonstrate that bone and aorta express the components of vitamin K cycle and of MK-4 synthesis. We also show the existence of a different gene expression pattern in AS progression in bone and aorta. These data might lead to a more comprehensive insight into the role of vitamin K metabolising enzymes in vascular calcification.