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

Daniel Scheiber, Verena Veulemans, Patrick Horn, Martijn L. Chatrou, Sebastian A. Potthoff, Malte Kelm, Leon J. Schurgers, Ralf Westenfeld*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

37 Citations (Web of Science)

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 mu g/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.
Original languageEnglish
Pages (from-to)6991-7011
JournalNutrients
Volume7
Issue number8
DOIs
Publication statusPublished - Aug 2015

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