Pathophysiological calcification in the vasculature favours cardio- and cerebrovascular diseases (CVD). In patients with chronic kidney disease, vitamin K metabolites, particularly K1 and MK-4, are associated with decreased vascular calcification. 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 to identify differences in expression pattern during atherosclerosis stages in aortic vascular tissue and to compare these profiles in both tissue types. Predesigned TaqMan gene expression assays were used on a LC480 system to determine gene expression in both tissue types. Determination of calcification stages was done histologically: (0 [unaffected vessels], 1 [intima thickening], 2 [intima calcification]). Both the VKC enzymes (VKOR, VKORL1, GGCX, the chaperone calu) and the enzymes necessary for MKS (NQO1 and UBIAD1) are expressed in aortic and bone tissue. In the aorta, gene expression of VKOR, VKORL1, and calu differed significantly among the three atherosclerotic stages (p=0.040; p=0.023 and p=0.038, respectively), whereas the expression of GGCX showed only borderline significance (p=0.060) between the three stages. In bone, gene expression of VKC and the MKS proteins did not differ in the three AS stages. Comparison of bone and aorta showed only significant differences in gene expression of calu, GGCX and NQO1 in stage 2. We showed that bone and aorta express the components of MK-4 synthesis as well as the vitamin K cycle. Furthermore, we could demonstrate that a different gene expression pattern exists in AS progression in bone and aorta. These data might shed light on the role of vitamin K metabolising enzymes in vascular calcification.
Disclosure: The authors declared no competing interests. Austrian National Bank (OeNB, grant number 13266), SFG (Comet K-project number 825329).