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

Scheiber D, Veulemans V, Horn P, Chatrou ML, Potthoff SA, Kelm M, Schurgers LJ, Westenfeld R - Nutrients (2015)

Bottom Line: 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.The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. daniel.scheiber@med.uni-duesseldorf.de.

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.

No MeSH data available.


Related in: MedlinePlus

Aortic gene expression. The effect of CKD and MK-7 supplementation on aortic gene expression of calcification modifiers as x-fold induction compared to control group. Red columns depict pro-calcific changes, while alterations associated with potential calcification inhibition are assigned with blue columns. (a) In CKD animals SM22α expression is significantly decreased, whereas MGP expression is non-significantly decreased as compared to Co animals. (b) In Co-K2 animals MGP mRNA concentration is significantly increased, whereas POST mRNA concentration is significantly decreased compared to Co animals. (c) In CKD-K2 animals MGP mRNA concentration is significantly and SM22α mRNA concentration is tendentially increased compared to Co animals. Co = control group; Co-K2 = MK-7 supplemented control group; CKD = 5/6 nephrectomized group; CKD-K2 = MK-7 supplemented 5/6 nephrectomized group; MGP = matrix Gla-protein; POST = periostin; BMP-2 = bone morphogenetic protein 2. Significant differences: *p < 0.05, **p < 0.01.
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nutrients-07-05318-f011: Aortic gene expression. The effect of CKD and MK-7 supplementation on aortic gene expression of calcification modifiers as x-fold induction compared to control group. Red columns depict pro-calcific changes, while alterations associated with potential calcification inhibition are assigned with blue columns. (a) In CKD animals SM22α expression is significantly decreased, whereas MGP expression is non-significantly decreased as compared to Co animals. (b) In Co-K2 animals MGP mRNA concentration is significantly increased, whereas POST mRNA concentration is significantly decreased compared to Co animals. (c) In CKD-K2 animals MGP mRNA concentration is significantly and SM22α mRNA concentration is tendentially increased compared to Co animals. Co = control group; Co-K2 = MK-7 supplemented control group; CKD = 5/6 nephrectomized group; CKD-K2 = MK-7 supplemented 5/6 nephrectomized group; MGP = matrix Gla-protein; POST = periostin; BMP-2 = bone morphogenetic protein 2. Significant differences: *p < 0.05, **p < 0.01.

Mentions: We analyzed regulation of relevant activators and inhibitors of VC in aortic tissue samples by quantitative real-time PCR. In a stepwise analysis, we investigated separately the effect of CKD (Figure 11a), MK-7 supplementation (Figure 11b), and finally the effect of MK-7 supplementation in CKD rats (Figure 11c), each compared to controls. For more clarity, pro-calcific changes are depicted by red columns while alterations associated with potential calcification inhibition are assigned with blue columns.


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

Scheiber D, Veulemans V, Horn P, Chatrou ML, Potthoff SA, Kelm M, Schurgers LJ, Westenfeld R - Nutrients (2015)

Aortic gene expression. The effect of CKD and MK-7 supplementation on aortic gene expression of calcification modifiers as x-fold induction compared to control group. Red columns depict pro-calcific changes, while alterations associated with potential calcification inhibition are assigned with blue columns. (a) In CKD animals SM22α expression is significantly decreased, whereas MGP expression is non-significantly decreased as compared to Co animals. (b) In Co-K2 animals MGP mRNA concentration is significantly increased, whereas POST mRNA concentration is significantly decreased compared to Co animals. (c) In CKD-K2 animals MGP mRNA concentration is significantly and SM22α mRNA concentration is tendentially increased compared to Co animals. Co = control group; Co-K2 = MK-7 supplemented control group; CKD = 5/6 nephrectomized group; CKD-K2 = MK-7 supplemented 5/6 nephrectomized group; MGP = matrix Gla-protein; POST = periostin; BMP-2 = bone morphogenetic protein 2. Significant differences: *p < 0.05, **p < 0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555157&req=5

nutrients-07-05318-f011: Aortic gene expression. The effect of CKD and MK-7 supplementation on aortic gene expression of calcification modifiers as x-fold induction compared to control group. Red columns depict pro-calcific changes, while alterations associated with potential calcification inhibition are assigned with blue columns. (a) In CKD animals SM22α expression is significantly decreased, whereas MGP expression is non-significantly decreased as compared to Co animals. (b) In Co-K2 animals MGP mRNA concentration is significantly increased, whereas POST mRNA concentration is significantly decreased compared to Co animals. (c) In CKD-K2 animals MGP mRNA concentration is significantly and SM22α mRNA concentration is tendentially increased compared to Co animals. Co = control group; Co-K2 = MK-7 supplemented control group; CKD = 5/6 nephrectomized group; CKD-K2 = MK-7 supplemented 5/6 nephrectomized group; MGP = matrix Gla-protein; POST = periostin; BMP-2 = bone morphogenetic protein 2. Significant differences: *p < 0.05, **p < 0.01.
Mentions: We analyzed regulation of relevant activators and inhibitors of VC in aortic tissue samples by quantitative real-time PCR. In a stepwise analysis, we investigated separately the effect of CKD (Figure 11a), MK-7 supplementation (Figure 11b), and finally the effect of MK-7 supplementation in CKD rats (Figure 11c), each compared to controls. For more clarity, pro-calcific changes are depicted by red columns while alterations associated with potential calcification inhibition are assigned with blue columns.

Bottom Line: 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.The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Duesseldorf, Duesseldorf 40225, Germany. daniel.scheiber@med.uni-duesseldorf.de.

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.

No MeSH data available.


Related in: MedlinePlus