Matrix Gla-protein: The calcification inhibitor in need of vitamin K

Matrix Gla-protein: The calcification inhibitor in need of vitamin K

Summary

Among the proteins involved in vascular calcium metabolism, the vitamin K-dependent matrix Gla-protein (MGP) plays a dominant role.Although on a molecular level its mechanism of action is not completely understood,it is generally accepted that MGP is a potent inhibitor of arterial calcification. Its pivotal importance for vascular health is demonstrated by the fact that there seems to be no effective alternative mechanism for calcification inhibition in the vasculature.An optimal vitamin K intake is therefore important to maintain the risk and rate of calcification as low as possible.With the aid of conformation-specific antibodies MGP species in both tissue and the circulation have been detected in the healthy population, and significant differences were found in patients with cardiovascular disease (CVD). Using ELISA-based assays, uncarboxylated MGP (ucMGP) was demonstrated to be a promising biomarker for cardiovascular calcification detection.These assays may have potential value for identifying patients as well as apparently healthy subjects at high risk for CVD and/or cardiovascular calcification and for monitoring the treatment of CVD and vascular calcification.

Source:Thromb Haemost. 2008 Oct;100(4):593-603. https://www.ncbi.nlm.nih.gov/pubmed/18841280<>

Adequate intake of menaquinone could be important for CHD prevention

Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study

ABSTRACT

Vitamin K–dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990–1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.

Source:J Nutr. 2004 Nov;134(11):3100-5. https://www.ncbi.nlm.nih.gov/pubmed/15514282

 

MK-7:Prevention of bone deterioration with aging

Stimulatory effect of menaquinone-7 on bone formation in elderly female rat femoral tissues in vitro: prevention of bone deterioration with aging.

Abstract

Menaquinone-7 (MK-7) is vitamin K2 which is a series of vitamins with multi-isoprene units at the 3-position of the naphthoquinone. MK-7 has been shown to prevent bone loss in ovariectomized rats, an animal model for osteoporosis.

This study was undertaken to determine whether MK-7 has a stimulatory effect on bone components of elderly female rats in vitro. The femoral-diaphyseal and -metaphyseal tissues obtained from young (4 weeks old) or elderly (50 weeks old) female rats were cultured for 48 h in a Dullbecco's modified Eagle's medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin.

Calcium content, alkaline phosphatase activity and deoxyribonucleic acid (DNA) in the diaphyseal and metaphyseal tissues obtained from elderly rats were significantly decreased as compared with those of young rats, indicating that aging causes a deterioration of bone formation.

The presence of MK-7 (10-6 or 10-5 M) caused a significant increase in biochemical components in the femoral-diaphyseal and -metaphyseal tissues obtained from elderly rat in vitro. The anabolic effect of MK-7 (10-6 or 10-5 M) on the femoral calcium content was significantly enhanced in the presence of phytoestrogen genistein (10-6 or 10-5 M), suggesting that the mode of action of MK-7 differ from that of genistein. The effect of MK-7 (10-5 M) in increasing calcium content, alkaline phosphatase activity and DNA content in the diaphyseal and metaphyseal tissues was completely abolished in the presence of cycloheximide (10-6 M), an inhibitor of protein synthesis in vitro. These findings demonstrate that MK-7 has a stimulatory effect on bone formation in the femoral tissues of elderly female rats in vitro. MK-7 may have a preventive role for bone deterioration with aging.

Source: INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 10: 729-733, 2002

 

Vitamin K2: Putting Calcium Where It Belongs

Vitamin K2: Putting Calcium Where It Belongs

Vitamin K2 provides major protection from osteoporosis, cardiovascular blockages and pathological calcification.

Vitamin K’s job is to put calcium in the right places and keep it from being deposited in the wrong places. The right places are bones and blood, and the wrong places include calcification of the vessels, bone spurs and calcification of soft tissues. 

Source: http://www.springboard4health.com/notebook/v_k2.html

 

 

Vitamin K2 in the prevention of hepatocellular carcinoma in women with viral cirrhosis.

Role of Vitamin K2 in the Development of Hepatocellular Carcinoma in Women With Viral Cirrhosis of the Liver

Context Previous findings indicate that vitamin K2 (menaquinone) may play a role in controlling cell growth.

Objective To determine whether vitamin K2 has preventive effects on the development of hepatocellular carcinoma in women with viral cirrhosis of the liver.

Design, Setting, and Participants Forty women diagnosed as having viral liver cirrhosis were admitted to a university hospital between 1996 and 1998 and were randomly assigned to the treatment or control group. The original goal of the trial was to assess the long-term effects of vitamin K2 on bone loss in women with viral liver cirrhosis. However, study participants also satisfied criteria required for examination of the effects of such treatment on the development of hepatocellular carcinoma.

Interventions The treatment group received 45 mg/d of vitamin K2 (n=21). Participants in the treatment and control groups received symptomatic therapy to treat ascites, if necessary, and dietary advice.

Main Outcome Measure Cumulative proportion of patients with hepatocellular carcinoma.

Results Hepatocellular carcinoma was detected in 2 of the 21 women given vitamin K2 and 9 of the 19 women in the control group. The cumulative proportion of patients with hepatocellular carcinoma was smaller in the treatment group (log-rank test, P=.02). On univariate analysis, the risk ratio for the development of hepatocellular carcinoma in the treatment group compared with the control group was 0.20 (95% confidence interval [CI], 0.04-0.91; P=.04). On multivariate analysis with adjustment for age, alanine aminotransferase activity, serum albumin, total bilirubin, platelet count, -fetoprotein, and history of treatment with interferon alfa, the risk ratio for the development of hepatocellular carcinoma in patients given vitamin K2 was 0.13 (95% CI, 0.02-0.99; P=.05). Conclusion There is a possible role for vitamin K2 in the prevention of hepatocellular carcinoma in women with viral cirrhosis.

Source: JAMA. 2004;292:358-361

 

 

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