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Carence en vitamine K et polymorphisme du gène Vkorc1 chez le rat : vers un nouveau modèle d’étude des calcifications vasculaires

Abstract : Vitamin K allows the biological activation of 14 proteins identified to date and called K-dependent vitamins (PVKD). A highly efficient recycling of vitamin K by the enzyme VKORC1 greatly limits the nutritional requirements. In some people, subcarence may exist and contribute to the development of vascular wall medial calcification and thus increase the cardiovascular risk factor. This type of calcification is found in people with hemodialysis, diabetes or simply during aging. The link between this subcarence and vascular calcification is difficult to study in humans because of a slow evolution and effects that can be masked by other environmental factors. To study this phenomenon directly, a murine model has been developed and characterized. The rats developed in this model have a greatly increased need for vitamin K because of a highly altered recycling. After 12 weeks of vitamin K deficiency, male rats had significant medial vascular calcification of the aorta, lungs, testes and heart. Coagulation is maintained although a decrease in activity of vitamin K-dependent coagulation factors is observed. Matrix-gla-tissue protein as well as plasma osteocalcin are found accumulated in their inactive form. At the same time, the concentration of tissue vitamin K is greatly reduced. These results are not observed in the non-mutated subcarenated rats nor in the non-subcarated mutated rats. This work allows for the first time to show the existence of a strong link between vitamin K subcarence and vascular calcifications. This subcarency model could be used to better understand the role of the different extrahepatic PVKDs. It is also a model of choice for the study of medial calcifications and their evolution
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Submitted on : Wednesday, September 4, 2019 - 12:17:25 PM
Last modification on : Wednesday, September 8, 2021 - 11:12:02 AM
Long-term archiving on: : Thursday, February 6, 2020 - 5:34:54 AM


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  • HAL Id : tel-02278326, version 1



Arnaud Michaux. Carence en vitamine K et polymorphisme du gène Vkorc1 chez le rat : vers un nouveau modèle d’étude des calcifications vasculaires. Biochimie, Biologie Moléculaire. Université de Lyon, 2018. Français. ⟨NNT : 2018LYSE1036⟩. ⟨tel-02278326⟩



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