Zinc Ameliorates the Osteogenic Effects of High Glucose in Vascular Smooth Muscle Cells

In diabetic patients, medial vascular calcification is common and associated with increased cardiovascular mortality. Excessive glucose concentrations can activate the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB) and trigger pro-calcific effects in vascular smooth muscle ce...

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Autores principales:	Laura A. Henze, Misael Estepa, Burkert Pieske, Florian Lang, Kai-Uwe Eckardt, Ioana Alesutan, Jakob Voelkl
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	diabetes mellitus GPR39 high glucose osteogenic transition vascular calcification vascular smooth muscle cells Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d98b8be4ed9044159ba4b33fea3f0613
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spelling	oai:doaj.org-article:d98b8be4ed9044159ba4b33fea3f06132021-11-25T17:11:19ZZinc Ameliorates the Osteogenic Effects of High Glucose in Vascular Smooth Muscle Cells10.3390/cells101130832073-4409https://doaj.org/article/d98b8be4ed9044159ba4b33fea3f06132021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3083https://doaj.org/toc/2073-4409In diabetic patients, medial vascular calcification is common and associated with increased cardiovascular mortality. Excessive glucose concentrations can activate the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB) and trigger pro-calcific effects in vascular smooth muscle cells (VSMCs), which may actively augment vascular calcification. Zinc is able to mitigate phosphate-induced VSMC calcification. Reduced serum zinc levels have been reported in diabetes mellitus. Therefore, in this study the effects of zinc supplementation were investigated in primary human aortic VSMCs exposed to excessive glucose concentrations. Zinc treatment was found to abrogate the stimulating effects of high glucose on VSMC calcification. Furthermore, zinc was found to blunt the increased expression of osteogenic and chondrogenic markers in high glucose-treated VSMCs. High glucose exposure was shown to activate NF-kB in VSMCs, an effect that was blunted by additional zinc treatment. Zinc was further found to increase the expression of TNFα-induced protein 3 (TNFAIP3) in high glucose-treated VSMCs. The silencing of TNFAIP3 was shown to abolish the protective effects of zinc on high glucose-induced NF-kB-dependent transcriptional activation, osteogenic marker expression, and the calcification of VSMCs. Silencing of the zinc-sensing receptor G protein-coupled receptor 39 (GPR39) was shown to abolish zinc-induced <i>TNFAIP3</i> expression and the effects of zinc on high glucose-induced osteogenic marker expression. These observations indicate that zinc may be a protective factor during vascular calcification in hyperglycemic conditions.Laura A. HenzeMisael EstepaBurkert PieskeFlorian LangKai-Uwe EckardtIoana AlesutanJakob VoelklMDPI AGarticlediabetes mellitusGPR39high glucoseosteogenic transitionvascular calcificationvascular smooth muscle cellsBiology (General)QH301-705.5ENCells, Vol 10, Iss 3083, p 3083 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetes mellitus GPR39 high glucose osteogenic transition vascular calcification vascular smooth muscle cells Biology (General) QH301-705.5
spellingShingle	diabetes mellitus GPR39 high glucose osteogenic transition vascular calcification vascular smooth muscle cells Biology (General) QH301-705.5 Laura A. Henze Misael Estepa Burkert Pieske Florian Lang Kai-Uwe Eckardt Ioana Alesutan Jakob Voelkl Zinc Ameliorates the Osteogenic Effects of High Glucose in Vascular Smooth Muscle Cells
description	In diabetic patients, medial vascular calcification is common and associated with increased cardiovascular mortality. Excessive glucose concentrations can activate the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB) and trigger pro-calcific effects in vascular smooth muscle cells (VSMCs), which may actively augment vascular calcification. Zinc is able to mitigate phosphate-induced VSMC calcification. Reduced serum zinc levels have been reported in diabetes mellitus. Therefore, in this study the effects of zinc supplementation were investigated in primary human aortic VSMCs exposed to excessive glucose concentrations. Zinc treatment was found to abrogate the stimulating effects of high glucose on VSMC calcification. Furthermore, zinc was found to blunt the increased expression of osteogenic and chondrogenic markers in high glucose-treated VSMCs. High glucose exposure was shown to activate NF-kB in VSMCs, an effect that was blunted by additional zinc treatment. Zinc was further found to increase the expression of TNFα-induced protein 3 (TNFAIP3) in high glucose-treated VSMCs. The silencing of TNFAIP3 was shown to abolish the protective effects of zinc on high glucose-induced NF-kB-dependent transcriptional activation, osteogenic marker expression, and the calcification of VSMCs. Silencing of the zinc-sensing receptor G protein-coupled receptor 39 (GPR39) was shown to abolish zinc-induced <i>TNFAIP3</i> expression and the effects of zinc on high glucose-induced osteogenic marker expression. These observations indicate that zinc may be a protective factor during vascular calcification in hyperglycemic conditions.
format	article
author	Laura A. Henze Misael Estepa Burkert Pieske Florian Lang Kai-Uwe Eckardt Ioana Alesutan Jakob Voelkl
author_facet	Laura A. Henze Misael Estepa Burkert Pieske Florian Lang Kai-Uwe Eckardt Ioana Alesutan Jakob Voelkl
author_sort	Laura A. Henze
title	Zinc Ameliorates the Osteogenic Effects of High Glucose in Vascular Smooth Muscle Cells
title_short	Zinc Ameliorates the Osteogenic Effects of High Glucose in Vascular Smooth Muscle Cells
title_full	Zinc Ameliorates the Osteogenic Effects of High Glucose in Vascular Smooth Muscle Cells
title_fullStr	Zinc Ameliorates the Osteogenic Effects of High Glucose in Vascular Smooth Muscle Cells
title_full_unstemmed	Zinc Ameliorates the Osteogenic Effects of High Glucose in Vascular Smooth Muscle Cells
title_sort	zinc ameliorates the osteogenic effects of high glucose in vascular smooth muscle cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d98b8be4ed9044159ba4b33fea3f0613
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Zinc Ameliorates the Osteogenic Effects of High Glucose in Vascular Smooth Muscle Cells

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