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Special Issue "Vitamin K in Human Health and Disease"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: 30 June 2018

Special Issue Editors

Guest Editor
Prof. Dr. Guylaine Ferland

Research Centre, Montreal Heart Institute, Université de Montréal, Montreal, QC H1T 1C8, Canada
Website | E-Mail
Interests: nutrition; vitamin K metabolism; ageing; brain function; Alzheimer’s disease; cardiovascular disease; nutrition interventions; nutrition requirements
Guest Editor
Dr. Mathieu Ferron

Institut de Recherches Cliniques de Montréal, Université de Montréal & Research Unit, Montreal, PQ H2W 1R7, Canada
Website | E-Mail
Interests: vitamin K; vitamin K reductases; protein gamma-carboxylation; bone metabolism; glucose metabolism; insulin secretion; insulin sensitivity

Special Issue Information

Dear Colleagues,

Initially discovered for its role in blood coagulation, it is now recognized that vitamin K (VK) is involved in many physiological systems besides hemostasis. Furthermore, it is now emerging that VK has biological and clinical roles that extend beyond its well-characterized action as an enzyme cofactor for the carboxylation of the VK-dependent proteins (VKDP). The aim of this Special Issue, entitled “Vitamin K in Human Health and Disease”, is to share the latest research findings on topics, such as (but not exclusively) the molecular aspects of VK cycle and metabolism (i.e., VKORC1, VKORC1L1), the VKDP as regards their emerging roles in energy metabolism and endocrine function (i.e., osteocalcin), the calcification process (i.e., matrix Gla protein) and brain function (i.e., Gas6), and the non-enzymatic role of menaquinone-4 (MK-4). These basic aspects of VK functions and metabolism will be discussed in the context of various chronic diseases, i.e., diabetes, CVD, CKD, cognitive impairment, and considering the modulatory role of VK nutritional status.

Prof. Dr. Guylaine Ferland
Dr. Mathieu Ferron
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Vitamin K (VK)
  • Menaquinone-4 (MK-4)
  • VKOR (VKORC1, VKORC1L1)
  • Vitamin K-dependent proteins (VKDP)
  • Matrix Gla protein
  • Osteocalcin
  • Calcification process
  • Endocrine function
  • Energy metabolism
  • Diabetes
  • Cardiovascular disease (CVD)
  • Chronic kidney disease (CKD)
  • Brain function

Published Papers (3 papers)

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Research

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Open AccessArticle Bicuspid Aortic Valve Stenosis and the Effect of Vitamin K2 on Calcification Using 18F-Sodium Fluoride Positron Emission Tomography/Magnetic Resonance: The BASIK2 Rationale and Trial Design
Nutrients 2018, 10(4), 386; doi:10.3390/nu10040386
Received: 6 February 2018 / Revised: 8 March 2018 / Accepted: 19 March 2018 / Published: 21 March 2018
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Abstract
BASIK2 is a prospective, double-blind, randomized placebo-controlled trial investigating the effect of vitamin K2 (menaquinone-7;MK7) on imaging measurements of calcification in the bicuspid aortic valve (BAV) and calcific aortic valve stenosis (CAVS). BAV is associated with early development of CAVS. Pathophysiologic mechanisms are
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BASIK2 is a prospective, double-blind, randomized placebo-controlled trial investigating the effect of vitamin K2 (menaquinone-7;MK7) on imaging measurements of calcification in the bicuspid aortic valve (BAV) and calcific aortic valve stenosis (CAVS). BAV is associated with early development of CAVS. Pathophysiologic mechanisms are incompletely defined, and the only treatment available is valve replacement upon progression to severe symptomatic stenosis. Matrix Gla protein (MGP) inactivity is suggested to be involved in progression. Being a vitamin K dependent protein, supplementation with MK7 is a pharmacological option for activating MGP and intervening in the progression of CAVS. Forty-four subjects with BAV and mild–moderate CAVS will be included in the study, and baseline 18F-sodiumfluoride (18F-NaF) positron emission tomography (PET)/ magnetic resonance (MR) and computed tomography (CT) assessments will be performed. Thereafter, subjects will be randomized (1:1) to MK7 (360 mcg/day) or placebo. During an 18-month follow-up period, subjects will visit the hospital every 6 months, undergoing a second 18F-NaF PET/MR after 6 months and CT after 6 and 18 months. The primary endpoint is the change in PET/MR 18F-NaF uptake (6 months minus baseline) compared to this delta change in the placebo arm. The main secondary endpoints are changes in calcium score (CT), progression of the left ventricularremodeling response and CAVS severity (echocardiography). We will also examine the association between early calcification activity (PET) and later changes in calcium score (CT). Full article
(This article belongs to the Special Issue Vitamin K in Human Health and Disease)
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Open AccessArticle Desphospho-Uncarboxylated Matrix-Gla Protein Is Increased Postoperatively in Cardiovascular Risk Patients
Nutrients 2018, 10(1), 46; doi:10.3390/nu10010046
Received: 15 November 2017 / Revised: 22 December 2017 / Accepted: 2 January 2018 / Published: 5 January 2018
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Abstract
Background: Matrix Gla protein (MGP) is an extrahepatic protein that is dependent on glutamate carboxylation, a vitamin K-dependent process. Its dysfunctional form, desphospho-uncarboxylated-MGP, has been associated with increased arterial calcification and stiffness. The aim of this study was to measure the degree of
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Background: Matrix Gla protein (MGP) is an extrahepatic protein that is dependent on glutamate carboxylation, a vitamin K-dependent process. Its dysfunctional form, desphospho-uncarboxylated-MGP, has been associated with increased arterial calcification and stiffness. The aim of this study was to measure the degree of postoperative carboxylation of MGP and two other Gla proteins in patients scheduled for abdominal or orthopaedic surgery. Methods: Forty patients undergoing abdominal or orthopaedic surgery were included. Blood samples were collected preoperatively and four days after the surgery. Desphospho-carboxylated MGP (dp-cMGP), desphospho-uncarboxylated MGP (dp-ucMGP), carboxylated osteocalcin (OC) (cOC), uncarboxylated OC (ucOC), and uncarboxylated prothrombin (PIVKA-II) were analysed. Results: Preoperatively, 29 patients had dp-ucMGP levels above the reference values. Patients with pre-existing cardiovascular comorbidities had higher dp-ucMGP preoperatively compared with patients with no record of cardiovascular disease. Postoperatively, this number increased to 36 patients, and median dp-ucMGP levels increased (p < 0.0001) and correlated to a PIVKA-II increase (r = 0.44). On the other hand, dp-cMGP levels did not significantly alter. Decreased levels of ucOC and cOC were seen after surgery (p = 0.017 and p = 0.0033, respectively). Comorbidities, possible nutritional defects, and complications affecting Gla protein activity and function were identified. Conclusions. Dp-ucMGP was high preoperatively, and had further increased postoperatively. This pattern was linked to several comorbidities, possible nutritional defects, and postoperative complications, which motivates further research about potential interactions between perioperative corrective treatments with vitamin K supplements, cardiovascular biomarkers, and incidents of stroke and myocardial infarction events. Full article
(This article belongs to the Special Issue Vitamin K in Human Health and Disease)
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Review

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Open AccessFeature PaperReview Is Matrix Gla Protein Associated with Vascular Calcification? A Systematic Review
Nutrients 2018, 10(4), 415; doi:10.3390/nu10040415
Received: 12 February 2018 / Revised: 13 March 2018 / Accepted: 23 March 2018 / Published: 27 March 2018
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Abstract
Specific patient cohorts are at increased risk of vascular calcification. Functional matrix-gla protein (MGP), a tissue-derived vitamin K dependent protein, is reported to be an important inhibitor of vascular calcification and may have clinical potential to modify the progression of vascular calcification through
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Specific patient cohorts are at increased risk of vascular calcification. Functional matrix-gla protein (MGP), a tissue-derived vitamin K dependent protein, is reported to be an important inhibitor of vascular calcification and may have clinical potential to modify the progression of vascular calcification through regulation of functional MGP fractions. This systematic review examines twenty-eight studies which assess the relationship between circulating protein expressions of MGP species and vascular calcification in different arterial beds. The included studies examined participants with atherosclerosis, chronic kidney disease (CKD), diabetes, healthy participants, vitamin K supplementation, measured plasma vitamin K levels and vitamin K antagonist usage. The current review reports conflicting results regarding MGP fractions with respect to local calcification development indicating that a multifaceted relationship exists between the MGP and calcification. A primary concern regarding the studies in this review is the large degree of variability in the calcification location assessed and the fraction of MGP measured. This review suggests that different underlying molecular mechanisms can accelerate local disease progression within the vasculature, and specific circulating fractions of MGP may be influenced differently depending on the local disease states related to vascular calcification development. Further studies examining the influence of non-functional MGP levels, with respect to specific calcified arterial beds, are warranted. Full article
(This article belongs to the Special Issue Vitamin K in Human Health and Disease)
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