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Vascular calcification: the price to pay for anticoagulation therapy with vitamin K-antagonists
Authors:Chatrou Martijn L L  Winckers Kristien  Hackeng Tilman M  Reutelingsperger Chris P  Schurgers Leon J
Affiliation:Department of Biochemistry, Cardiovascular Research Institute Maastricht, MUMC, Maastricht, The Netherlands.
Abstract:Vitamin K-antagonists (VKA) are the most widely used anti-thrombotic drugs with substantial efficacy in reducing risk of arterial and venous thrombosis. Several lines of evidence indicate, however, that VKA inhibit not only post-translational activation of vitamin K-dependent coagulation factors but also synthesis of functional extra-hepatic vitamin K-dependent proteins thereby eliciting undesired side-effects. Vascular calcification is one of the recently revealed side-effects of VKA. Vascular calcification is an actively regulated process involving vascular cells and a number of vitamin K-dependent proteins. Mechanistic understanding of vascular calcification is essential to improve VKA-based treatments of both thrombotic disorders and atherosclerosis. This review addresses vitamin K-cycle and vitamin K-dependent processes of vascular calcification that are affected by VKA. We conclude that there is a growing need for better understanding of the effects of anticoagulants on vascular calcification and atherosclerosis.
Keywords:VKA, vitamin K antagonists   MGP, matrix Gla protein   GGCX, γ-glutamylcarboxylase, enzyme responsible for carboxylation   Gla, γ-carboxyglutamic acid or γ-carboxyglutamate   Glu, glutamic acid   VKDP, vitamin K-dependent proteins   K, vitamin K-quinone   KH2, vitamin K hydro-quinone   KO, vitamin K 2,3-epoxide   VKOR, vitamin K-epoxide reductase, reducing enzyme for KH2   DT-diaphorase, quinone oxidoreductase, reducing enzyme for KH2   VKORC1, VKOR complex 1   CYP2C9, Cytochrome P450 2C9, cytochrome responsible for VKA metabolism   HDN, hemorrhagic disease of the newborn   VKDB, vitamin K-deficiency bleeding   OC, osteocalcin   Gas-6, growth arrest specific gene 6 protein   VSMCs, vascular smooth muscle cells   PCS, peak circumferential stress   ECM, extracellular matrix   MV, matrix vesicles, membrane shedded vesicles derived from viable cells   AB, apoptotic bodies, vesicular cell remnants of apoptotic cells   MSCT, multi-slice computed tomography   PIVKA-II, Protein Induced by Vitamin K Absence of Antagonism-Factor II   PARs, protease activated receptors   NOAC, novel oral anticoagulants
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