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PROJECT 15 

Modulating Vitamin K-dependent proteins targeting Vascular calcification. 

PROJECT DESCRIPTION

Objectives: 

We will test the hypothesis that vitamin K-metabolism (deficiency induced by either disease, food or drug or treatment with supplemental vitamin K) is a major mediator of vascular calcification and plaque vulnerability. We will measure phosphorylation and carboxylation status of matrix Gla-protein in patient samples. Finally, we will test effects of interventions (vitamin K-supplementation, drug intervention) on vascular calcification and remodelling.


Methodologies: 

VitaVasK and VitaK-CAC are both prospective, randomized multicentre trials (EudraCT No.: 2010-021264-14; NCT01002157). VitaVasK will include 348 HD patients in an open-label, two-arm design. VitaK-CAC includes 180 patients with CAC in a double blind, placebo controlled manner (currently 150 patients, inclusion finished June 2016). After baseline multi-slice computed tomography (MSCT) of the heart and thoracic aorta, patients with a coronary calcification volume score > 50 will be randomized to continue on standard care or to receive additional supplementation with vitamin K. Plasma will be available from these patients. Different MGP conformations will be analysed using ELISA based assays. In collaboration with ESR3 plasma or serum will be tested using the xCELLigence system for VSMCs and in ESR2 on endothelial cells. Biobank samples, both tissue and plasma will be tested in connection with ESR8. Cell functions will be assessed by multiplex fluorescence analyses using in-house produced cell-function-reporters. We will test plasma or serum obtained from patients on different OAC and vitamin K regimens on primary human endothelial and VSMC cells.

Host institution

Universitätsklinikum Aachen (Germany)

Prof. Jürgen Floege