title: The realm of vitamin K dependent proteins: shifting from coagulation toward calcification.
abstract: In the past few decades vitamin K has emerged from a single-function "haemostasis vitamin" to a "multi-function vitamin." The use of vitamin K antagonists (VKA) inevitably showed that the inhibition was not restricted to vitamin K dependent coagulation factors but also synthesis of functional extrahepatic vitamin K dependent proteins (VKDPs), thereby eliciting undesired side effects. Vascular calcification is one of the recently revealed detrimental effects of VKA. The discovery that VKDPs are involved in vascular calcification has propelled our mechanistic understanding of this process and has opened novel avenues for diagnosis and treatment. This review addresses mechanisms of VKDPs and their significance for physiological and pathological calcification.
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands; VitaK BV, Maastricht University, Maastricht, The Netherlands.
authors.forename: Brecht A G
authors.initials: BA
authors.lastname: Willems
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.forename: Chris P M
authors.initials: CP
authors.lastname: Reutelingsperger
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Schurgers
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D035843:Biomedical Research / Q000639:trends; D001777:Blood Coagulation / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D002114:Calcinosis / Q000209:etiology / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D008954:Models, Biological; D014812:Vitamin K / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D014813:Vitamin K Deficiency / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy
chemical_list: D000925:Anticoagulants; D014812:Vitamin K
keywords: Gla-rich protein; Matrix Gla protein; Osteocalcin; Vascular calcification; Vitamin K