High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification
by
Daniel Scheiber 1,†, Verena Veulemans 1,†, Patrick Horn 1, Martijn L. Chatrou 2, Sebastian A. Potthoff 3, Malte Kelm 1,4, Leon J. Schurgers 2,†
and Ralf Westenfeld 1,*,†
Daniel Scheiber 1,†, Verena Veulemans 1,†, Patrick Horn 1, Martijn L. Chatrou 2, Sebastian A. Potthoff 3, Malte Kelm 1,4, Leon J. Schurgers 2,† and Ralf Westenfeld 1,*,†
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
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Nutrients 2015, 7(8), 6991-7011; https://doi.org/10.3390/nu7085318
Received: 15 May 2015 / Revised: 30 July 2015 / Accepted: 6 August 2015 / Published: 18 August 2015
(This article belongs to the Special Issue Vitamin K and Vitamin K-Dependent Proteins in Relation to Human Health)
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.
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Keywords:
menaquinone-7; vitamin K2; cardiovascular calcification; matrix Gla-protein; chronic kidney disease
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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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