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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

Proliferative response. Ratio of positive staining area for Ki67 per DAPI positive staining area in % per mm2. DAPI values do not differ significantly between groups. CKD animals display significantly more Ki67 positive staining area per DAPI positive staining area 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; mm = millimeters. Significant differences: ***p < 0.001.
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nutrients-07-05318-f008: Proliferative response. Ratio of positive staining area for Ki67 per DAPI positive staining area in % per mm2. DAPI values do not differ significantly between groups. CKD animals display significantly more Ki67 positive staining area per DAPI positive staining area 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; mm = millimeters. Significant differences: ***p < 0.001.

Mentions: Proliferative response: Immunofluorescence staining of Ki67/DAPI revealed markedly increased cell proliferation in CKD and CKD-K2 animals compared to controls (CKD vs. Co, p < 0.001). MK-7 supplementation did not alter the proliferative response to the CKD stimulus (Figure 8).


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)

Proliferative response. Ratio of positive staining area for Ki67 per DAPI positive staining area in % per mm2. DAPI values do not differ significantly between groups. CKD animals display significantly more Ki67 positive staining area per DAPI positive staining area 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; mm = millimeters. Significant differences: ***p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

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

nutrients-07-05318-f008: Proliferative response. Ratio of positive staining area for Ki67 per DAPI positive staining area in % per mm2. DAPI values do not differ significantly between groups. CKD animals display significantly more Ki67 positive staining area per DAPI positive staining area 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; mm = millimeters. Significant differences: ***p < 0.001.
Mentions: Proliferative response: Immunofluorescence staining of Ki67/DAPI revealed markedly increased cell proliferation in CKD and CKD-K2 animals compared to controls (CKD vs. Co, p < 0.001). MK-7 supplementation did not alter the proliferative response to the CKD stimulus (Figure 8).

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