Endothelial Contribution to Warfarin-Induced Arterial Media Calcification in Mice

Arterial media calcification (AMC) is predominantly regulated by vascular smooth muscle cells (VSMCs), which transdifferentiate into pro-calcifying cells. In contrast, there is little evidence for endothelial cells playing a role in the disease. The current study investigates cellular functioning an...

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Autores principales:	Geoffrey Van den Bergh, Sofie De Moudt, Astrid Van den Branden, Ellen Neven, Hanne Leysen, Stuart Maudsley, Guido R. Y. De Meyer, Patrick D’Haese, Anja Verhulst
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	vascular calcification endothelial cells vascular smooth muscle cells nitric oxide organ baths Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/8b898170d6e54520be4e38351853648f
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spelling	oai:doaj.org-article:8b898170d6e54520be4e38351853648f2021-11-11T17:05:36ZEndothelial Contribution to Warfarin-Induced Arterial Media Calcification in Mice10.3390/ijms2221116151422-00671661-6596https://doaj.org/article/8b898170d6e54520be4e38351853648f2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11615https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Arterial media calcification (AMC) is predominantly regulated by vascular smooth muscle cells (VSMCs), which transdifferentiate into pro-calcifying cells. In contrast, there is little evidence for endothelial cells playing a role in the disease. The current study investigates cellular functioning and molecular pathways underlying AMC, respectively by, an ex vivo isometric organ bath set-up to explore the interaction between VSMCs and ECs and quantitative proteomics followed by functional pathway interpretation. AMC development, which was induced in mice by dietary warfarin administration, was proved by positive Von Kossa staining and a significantly increased calcium content in the aorta compared to that of control mice. The ex vivo organ bath set-up showed calcified aortic segments to be significantly more sensitive to phenylephrine induced contraction, compared to control segments. This, together with the fact that calcified segments as compared to control segments, showed a significantly smaller contraction in the absence of extracellular calcium, argues for a reduced basal NO production in the calcified segments. Moreover, proteomic data revealed a reduced eNOS activation to be part of the vascular calcification process. In summary, this study identifies a poor endothelial function, next to classic pro-calcifying stimuli, as a possible initiator of arterial calcification.Geoffrey Van den BerghSofie De MoudtAstrid Van den BrandenEllen NevenHanne LeysenStuart MaudsleyGuido R. Y. De MeyerPatrick D’HaeseAnja VerhulstMDPI AGarticlevascular calcificationendothelial cellsvascular smooth muscle cellsnitric oxideorgan bathsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11615, p 11615 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	vascular calcification endothelial cells vascular smooth muscle cells nitric oxide organ baths Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	vascular calcification endothelial cells vascular smooth muscle cells nitric oxide organ baths Biology (General) QH301-705.5 Chemistry QD1-999 Geoffrey Van den Bergh Sofie De Moudt Astrid Van den Branden Ellen Neven Hanne Leysen Stuart Maudsley Guido R. Y. De Meyer Patrick D’Haese Anja Verhulst Endothelial Contribution to Warfarin-Induced Arterial Media Calcification in Mice
description	Arterial media calcification (AMC) is predominantly regulated by vascular smooth muscle cells (VSMCs), which transdifferentiate into pro-calcifying cells. In contrast, there is little evidence for endothelial cells playing a role in the disease. The current study investigates cellular functioning and molecular pathways underlying AMC, respectively by, an ex vivo isometric organ bath set-up to explore the interaction between VSMCs and ECs and quantitative proteomics followed by functional pathway interpretation. AMC development, which was induced in mice by dietary warfarin administration, was proved by positive Von Kossa staining and a significantly increased calcium content in the aorta compared to that of control mice. The ex vivo organ bath set-up showed calcified aortic segments to be significantly more sensitive to phenylephrine induced contraction, compared to control segments. This, together with the fact that calcified segments as compared to control segments, showed a significantly smaller contraction in the absence of extracellular calcium, argues for a reduced basal NO production in the calcified segments. Moreover, proteomic data revealed a reduced eNOS activation to be part of the vascular calcification process. In summary, this study identifies a poor endothelial function, next to classic pro-calcifying stimuli, as a possible initiator of arterial calcification.
format	article
author	Geoffrey Van den Bergh Sofie De Moudt Astrid Van den Branden Ellen Neven Hanne Leysen Stuart Maudsley Guido R. Y. De Meyer Patrick D’Haese Anja Verhulst
author_facet	Geoffrey Van den Bergh Sofie De Moudt Astrid Van den Branden Ellen Neven Hanne Leysen Stuart Maudsley Guido R. Y. De Meyer Patrick D’Haese Anja Verhulst
author_sort	Geoffrey Van den Bergh
title	Endothelial Contribution to Warfarin-Induced Arterial Media Calcification in Mice
title_short	Endothelial Contribution to Warfarin-Induced Arterial Media Calcification in Mice
title_full	Endothelial Contribution to Warfarin-Induced Arterial Media Calcification in Mice
title_fullStr	Endothelial Contribution to Warfarin-Induced Arterial Media Calcification in Mice
title_full_unstemmed	Endothelial Contribution to Warfarin-Induced Arterial Media Calcification in Mice
title_sort	endothelial contribution to warfarin-induced arterial media calcification in mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8b898170d6e54520be4e38351853648f
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Endothelial Contribution to Warfarin-Induced Arterial Media Calcification in Mice

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