Missense mutation of VKORC1 leads to medial arterial calcification in rats

Abstract Vitamin K plays a crucial role in the regulation of vascular calcifications by allowing activation of matrix Gla protein. The dietary requirement for vitamin K is low because of an efficient recycling of vitamin K by vitamin K epoxide reductase (VKORC1). However, decreased VKORC1 activity m...

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Autores principales:	Arnaud Michaux, Benjamin Matagrin, Jean-Valéry Debaux, Leon J. Schurgers, Etienne Benoit, Virginie Lattard
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medial Arterial Calcification Vascular Calcification Anticoagulant Resistance Matrix Gla Protein (MGP) Limited Uptake Medicine R Science Q
Acceso en línea:	https://doaj.org/article/522f54e8dff545d79a3fde7d87d7e393
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spelling	oai:doaj.org-article:522f54e8dff545d79a3fde7d87d7e3932021-12-02T15:08:05ZMissense mutation of VKORC1 leads to medial arterial calcification in rats10.1038/s41598-018-31788-62045-2322https://doaj.org/article/522f54e8dff545d79a3fde7d87d7e3932018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31788-6https://doaj.org/toc/2045-2322Abstract Vitamin K plays a crucial role in the regulation of vascular calcifications by allowing activation of matrix Gla protein. The dietary requirement for vitamin K is low because of an efficient recycling of vitamin K by vitamin K epoxide reductase (VKORC1). However, decreased VKORC1 activity may result in vascular calcification. More than 30 coding mutations of VKORC1 have been described. While these mutations have been suspected of causing anticoagulant resistance, their association with an increase in the risk of vascular calcification has never been considered. We thus investigated functional cardiovascular characteristics in a rat model mutated in VKORC1. This study revealed that limited intake in vitamin K in mutated rat induced massive calcified areas in the media of arteries of lung, aortic arch, kidneys and testis. Development of calcifications could be inhibited by vitamin K supplementation. In calcified areas, inactive Matrix Gla protein expression increased, while corresponding mRNA expression was not modified. Mutation in VKORC1 associated with a limited vitamin K intake is thus a major risk for cardiovascular disease. Our model is the first non-invasive rat model that shows spontaneous medial calcifications and would be useful for studying physiological function of vitamin K.Arnaud MichauxBenjamin MatagrinJean-Valéry DebauxLeon J. SchurgersEtienne BenoitVirginie LattardNature PortfolioarticleMedial Arterial CalcificationVascular CalcificationAnticoagulant ResistanceMatrix Gla Protein (MGP)Limited UptakeMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medial Arterial Calcification Vascular Calcification Anticoagulant Resistance Matrix Gla Protein (MGP) Limited Uptake Medicine R Science Q
spellingShingle	Medial Arterial Calcification Vascular Calcification Anticoagulant Resistance Matrix Gla Protein (MGP) Limited Uptake Medicine R Science Q Arnaud Michaux Benjamin Matagrin Jean-Valéry Debaux Leon J. Schurgers Etienne Benoit Virginie Lattard Missense mutation of VKORC1 leads to medial arterial calcification in rats
description	Abstract Vitamin K plays a crucial role in the regulation of vascular calcifications by allowing activation of matrix Gla protein. The dietary requirement for vitamin K is low because of an efficient recycling of vitamin K by vitamin K epoxide reductase (VKORC1). However, decreased VKORC1 activity may result in vascular calcification. More than 30 coding mutations of VKORC1 have been described. While these mutations have been suspected of causing anticoagulant resistance, their association with an increase in the risk of vascular calcification has never been considered. We thus investigated functional cardiovascular characteristics in a rat model mutated in VKORC1. This study revealed that limited intake in vitamin K in mutated rat induced massive calcified areas in the media of arteries of lung, aortic arch, kidneys and testis. Development of calcifications could be inhibited by vitamin K supplementation. In calcified areas, inactive Matrix Gla protein expression increased, while corresponding mRNA expression was not modified. Mutation in VKORC1 associated with a limited vitamin K intake is thus a major risk for cardiovascular disease. Our model is the first non-invasive rat model that shows spontaneous medial calcifications and would be useful for studying physiological function of vitamin K.
format	article
author	Arnaud Michaux Benjamin Matagrin Jean-Valéry Debaux Leon J. Schurgers Etienne Benoit Virginie Lattard
author_facet	Arnaud Michaux Benjamin Matagrin Jean-Valéry Debaux Leon J. Schurgers Etienne Benoit Virginie Lattard
author_sort	Arnaud Michaux
title	Missense mutation of VKORC1 leads to medial arterial calcification in rats
title_short	Missense mutation of VKORC1 leads to medial arterial calcification in rats
title_full	Missense mutation of VKORC1 leads to medial arterial calcification in rats
title_fullStr	Missense mutation of VKORC1 leads to medial arterial calcification in rats
title_full_unstemmed	Missense mutation of VKORC1 leads to medial arterial calcification in rats
title_sort	missense mutation of vkorc1 leads to medial arterial calcification in rats
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/522f54e8dff545d79a3fde7d87d7e393
work_keys_str_mv	AT arnaudmichaux missensemutationofvkorc1leadstomedialarterialcalcificationinrats AT benjaminmatagrin missensemutationofvkorc1leadstomedialarterialcalcificationinrats AT jeanvalerydebaux missensemutationofvkorc1leadstomedialarterialcalcificationinrats AT leonjschurgers missensemutationofvkorc1leadstomedialarterialcalcificationinrats AT etiennebenoit missensemutationofvkorc1leadstomedialarterialcalcificationinrats AT virginielattard missensemutationofvkorc1leadstomedialarterialcalcificationinrats
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Missense mutation of VKORC1 leads to medial arterial calcification in rats

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