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Nutrients 2015, 7(8), 6991-7011; doi:10.3390/nu7085318

High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

1
Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany
2
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht 6229 ER, The Netherlands
3
Department of Nephrology, University Duesseldorf, Medical Faculty, Duesseldorf 40225, Germany
4
Cardiovascular Research Institute Duesseldorf, University Duesseldorf, Medical Faculty, Duesseldorf 40225, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 15 May 2015 / Revised: 30 July 2015 / Accepted: 6 August 2015 / Published: 18 August 2015
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Abstract

Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures. View Full-Text
Keywords: menaquinone-7; vitamin K2; cardiovascular calcification; matrix Gla-protein; chronic kidney disease menaquinone-7; vitamin K2; cardiovascular calcification; matrix Gla-protein; chronic kidney disease
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Scheiber, D.; Veulemans, V.; Horn, P.; Chatrou, M.L.; Potthoff, S.A.; Kelm, M.; Schurgers, L.J.; Westenfeld, R. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification. Nutrients 2015, 7, 6991-7011.

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