Role of vitamin K and vitamin K-dependent proteins in vascular calcification

Schurgers, Leon J.; Dissel, P.E.P.; Spronk, Henri M. H.; Soute, Berry A.M.; Dhore, C.R.; Cleutjens, J. P. M.; Vermeer, Cees

doi:10.1007/s003920170043

Cited by 62 publications

(55 citation statements)

References 39 publications

(42 reference statements)

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“…MGP expression was found to be increased especially in lipid-rich areas of plaques and seemed to surround calcifying areas [10]. These data were consistent with immunohistochemical data in which MGP in atherosclerotic arteries was stained using a monoclonal antibody against human MGP [19,20]. It is thought that local MGP upregulation may be a central mechanism counteracting and thus limiting excessive vascular calcification.…”

Section: Calcium-regulatory Proteins and Extraosseus Calcificationsupporting

confidence: 78%

Novel Insights into Uremic Vascular Calcification: Role of Matrix Gla Protein and Alpha-2-Heremans Schmid Glycoprotein/Fetuin

Ketteler

Vermeer²,

Wanner³

et al. 2002

Blood Purif

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Cardiovascular mortality is markedly increased in the dialysis population when compared to non-uremic subjects. Vascular and valvular calcifications are most frequently found in dialysis patients at risk and are independent predictors of cardiovascular death in this population. Traditionally, the presence of hyperphosphatemia and an increased calcium × phosphate product was considered a major pathomechanistic condition leading to excessive vascular and soft-tissue calcifications in uremic subjects. Recent studies in knockout mice, however, revealed that deficiencies in calcium-regulatory proteins may also directly contribute to the development of extraosseus calcifications. α₂-Heremans Schmid glycoprotein and matrix Gla protein are important inhibitors of calcification in vivo and there is novel evidence available that a deficiency in such proteins is involved in the pathogenesis of cardiovascular calcifications in dialysis patients.

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Section: Calcium-regulatory Proteins and Extraosseus Calcificationsupporting

confidence: 78%

Novel Insights into Uremic Vascular Calcification: Role of Matrix Gla Protein and Alpha-2-Heremans Schmid Glycoprotein/Fetuin

Ketteler

Vermeer²,

Wanner³

et al. 2002

Blood Purif

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“…This indicates that MGP plays an important role in the inhibition of vascular calcification. The ␥ -glutamyl carboxylation of MGP is essential for its inhibitory effect on calcification in vitro [28] , and in vivo, undercarboxylation of MGP (ucMGP) is a risk factor for vascular calcification [29] . In the Rotterdam trial in 4,800 elderly patients, low vitamin K 2 intake was associated with a higher incidence of severe aortic calcification and increased mortality [30] .…”

Section: Discussionmentioning

confidence: 99%

Undercarboxylated Osteocalcin Is a Biomarker of Carotid Calcification in Patients with Essential Hypertension

Okura

Kurata

Enomoto

et al. 2010

Kidney Blood Press Res

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The development of vascular calcification is an active, highly regulated process with similarities to bone formation. Osteocalcin (OC), a vitamin K-dependent protein expressed by osteoblasts, contains 3 γ-carboxyglutamic acid residues derived from the vitamin K-dependent posttranslational modification of glutamic acid residues. Circulating undercarboxylated OC (ucOC) is increased in vitamin K deficiency and serum ucOC is reported to be a clinical marker of vitamin K status. Vitamin K deficiency is associated with vascular calcification as well as osteoporosis. We evaluated the relationship between ucOC and carotid artery calcification in 92 patients with essential hypertension. Ultrasound of the common carotid artery was performed to identify vascular calcification and subjects were divided into 2 groups: a calcification (+) group and a calcification (–) group. Serum creatinine and ucOC levels were higher in the calcification (+) group than in the calcification (–) group and serum ucOC correlated with serum creatinine. To identify the independent determinant factor for carotid artery calcification, we applied both ucOC and estimated glomerular filtration rate as independent factors in logistic regression analysis. Serum ucOC was an independent determinant of carotid calcification, suggesting that circulating ucOC may be an important biomarker of carotid artery calcification.

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“…In particular, low vitamin K intake has been associated with low bone mineral density (Booth et al, 2003a) and an increased fracture risk (Feskanich et al, 1999;Booth et al, 2000) and low plasma vitamin K status has been associated with an increased prevalence of osteoarthritis (Neogi et al, 2006). Evidence is also emerging for a benefit of increased vitamin K intake and status in reducing vascular calcification via the VKD protein, matrix Gla protein (Jie et al, 1995;Schurgers et al, 2001;Berkner and Runge, 2004).…”

Section: Introductionmentioning

confidence: 99%

A stable isotope method for the simultaneous measurement of vitamin K1 (phylloquinone) kinetics and absorption

et al. 2007

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Objectives: To measure uptake and disposal kinetics and absolute absorption of vitamin K 1 using two stable isotope-labelled forms of vitamin K 1 . Subjects: Ten subjects (nine women and one man) aged between 22 and 31 years, with a mean (7standard deviation) body mass index of 22.572.4 kg/m 2 . Subjects took capsules containing 3 mg of methyl-13 C vitamin K 1 , three times a day for six days to reach a steady state for plasma vitamin K 1 isotopic enrichment. On day seven, subjects were given an intravenous dose of Konakion MM to measure disposal kinetics and at the same time, a capsule containing 4 mg of ring-D 4 vitamin K 1 to measure absorption. Plasma vitamin K 1 concentration was measured by high-performance liquid chromatography and isotopic composition by gas chromatography mass spectrometry. Results: The disposal kinetics of the intravenous dose of vitamin K 1 were resolved into two exponentials with half-times of 0.22 (70.14) and 2.66 (71.69) h. Absorption of oral, deuterated vitamin K 1 was 13 (79) %. Conclusions: Two-compartmental kinetic parameters observed in this study are similar to those obtained previously using radioactive tracers, but there may be additional slow-turnover body pools acting as stores of vitamin K 1 . The kinetic parameters determined from the intravenous dose allowed determination of the absolute absorption of vitamin K 1 from a bolus oral dose.

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Role of vitamin K and vitamin K-dependent proteins in vascular calcification

Cited by 62 publications

References 39 publications

Novel Insights into Uremic Vascular Calcification: Role of Matrix Gla Protein and Alpha-2-Heremans Schmid Glycoprotein/Fetuin

Novel Insights into Uremic Vascular Calcification: Role of Matrix Gla Protein and Alpha-2-Heremans Schmid Glycoprotein/Fetuin

Undercarboxylated Osteocalcin Is a Biomarker of Carotid Calcification in Patients with Essential Hypertension

A stable isotope method for the simultaneous measurement of vitamin K1 (phylloquinone) kinetics and absorption

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