Carbamylation of elastic fibers is a molecular substratum of aortic stiffness

Abstract Because of their long lifespan, matrix proteins of the vascular wall, such as elastin, are subjected to molecular aging characterized by non-enzymatic post-translational modifications, like carbamylation which results from the binding of cyanate (mainly derived from the dissociation of urea...

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Autores principales:	Manon Doué, Anaïs Okwieka, Alexandre Berquand, Laëtitia Gorisse, Pascal Maurice, Frédéric Velard, Christine Terryn, Michaël Molinari, Laurent Duca, Christine Piétrement, Philippe Gillery, Stéphane Jaisson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7d9112e629014374850de6a0f738d8c7
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spelling	oai:doaj.org-article:7d9112e629014374850de6a0f738d8c72021-12-02T17:41:18ZCarbamylation of elastic fibers is a molecular substratum of aortic stiffness10.1038/s41598-021-97293-52045-2322https://doaj.org/article/7d9112e629014374850de6a0f738d8c72021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97293-5https://doaj.org/toc/2045-2322Abstract Because of their long lifespan, matrix proteins of the vascular wall, such as elastin, are subjected to molecular aging characterized by non-enzymatic post-translational modifications, like carbamylation which results from the binding of cyanate (mainly derived from the dissociation of urea) to protein amino groups. While several studies have demonstrated a relationship between increased plasma concentrations of carbamylated proteins and the development of cardiovascular diseases, molecular mechanisms explaining the involvement of protein carbamylation in these pathological contexts remain to be fully elucidated. The aim of this work was to determine whether vascular elastic fibers could be carbamylated, and if so, what impact this phenomenon would have on the mechanical properties of the vascular wall. Our experiments showed that vascular elastin was carbamylated in vivo. Fiber morphology was unchanged after in vitro carbamylation, as well as its sensitivity to elastase degradation. In mice fed with cyanate-supplemented water in order to increase protein carbamylation within the aortic wall, an increased stiffness in elastic fibers was evidenced by atomic force microscopy, whereas no fragmentation of elastic fiber was observed. In addition, this increased stiffness was also associated with an increase in aortic pulse wave velocity in ApoE−/− mice. These results provide evidence for the carbamylation of elastic fibers which results in an increase in their stiffness at the molecular level. These alterations of vessel wall mechanical properties may contribute to aortic stiffness, suggesting a new role for carbamylation in cardiovascular diseases.Manon DouéAnaïs OkwiekaAlexandre BerquandLaëtitia GorissePascal MauriceFrédéric VelardChristine TerrynMichaël MolinariLaurent DucaChristine PiétrementPhilippe GilleryStéphane JaissonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manon Doué Anaïs Okwieka Alexandre Berquand Laëtitia Gorisse Pascal Maurice Frédéric Velard Christine Terryn Michaël Molinari Laurent Duca Christine Piétrement Philippe Gillery Stéphane Jaisson Carbamylation of elastic fibers is a molecular substratum of aortic stiffness
description	Abstract Because of their long lifespan, matrix proteins of the vascular wall, such as elastin, are subjected to molecular aging characterized by non-enzymatic post-translational modifications, like carbamylation which results from the binding of cyanate (mainly derived from the dissociation of urea) to protein amino groups. While several studies have demonstrated a relationship between increased plasma concentrations of carbamylated proteins and the development of cardiovascular diseases, molecular mechanisms explaining the involvement of protein carbamylation in these pathological contexts remain to be fully elucidated. The aim of this work was to determine whether vascular elastic fibers could be carbamylated, and if so, what impact this phenomenon would have on the mechanical properties of the vascular wall. Our experiments showed that vascular elastin was carbamylated in vivo. Fiber morphology was unchanged after in vitro carbamylation, as well as its sensitivity to elastase degradation. In mice fed with cyanate-supplemented water in order to increase protein carbamylation within the aortic wall, an increased stiffness in elastic fibers was evidenced by atomic force microscopy, whereas no fragmentation of elastic fiber was observed. In addition, this increased stiffness was also associated with an increase in aortic pulse wave velocity in ApoE−/− mice. These results provide evidence for the carbamylation of elastic fibers which results in an increase in their stiffness at the molecular level. These alterations of vessel wall mechanical properties may contribute to aortic stiffness, suggesting a new role for carbamylation in cardiovascular diseases.
format	article
author	Manon Doué Anaïs Okwieka Alexandre Berquand Laëtitia Gorisse Pascal Maurice Frédéric Velard Christine Terryn Michaël Molinari Laurent Duca Christine Piétrement Philippe Gillery Stéphane Jaisson
author_facet	Manon Doué Anaïs Okwieka Alexandre Berquand Laëtitia Gorisse Pascal Maurice Frédéric Velard Christine Terryn Michaël Molinari Laurent Duca Christine Piétrement Philippe Gillery Stéphane Jaisson
author_sort	Manon Doué
title	Carbamylation of elastic fibers is a molecular substratum of aortic stiffness
title_short	Carbamylation of elastic fibers is a molecular substratum of aortic stiffness
title_full	Carbamylation of elastic fibers is a molecular substratum of aortic stiffness
title_fullStr	Carbamylation of elastic fibers is a molecular substratum of aortic stiffness
title_full_unstemmed	Carbamylation of elastic fibers is a molecular substratum of aortic stiffness
title_sort	carbamylation of elastic fibers is a molecular substratum of aortic stiffness
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7d9112e629014374850de6a0f738d8c7
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Carbamylation of elastic fibers is a molecular substratum of aortic stiffness

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