The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness

Abstract Stiffening of the aorta is an important independent risk factor for myocardial infarction and stroke. Yet its genetics is complex and little is known about its molecular drivers. We have identified for the first time, tagSNPs in the genes for extracellular matrix proteins, aggrecan and fibu...

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Autores principales:	Yasmin, Raya Al Maskari, Carmel M. McEniery, Sarah E. Cleary, Ye Li, Keith Siew, Nichola L. Figg, Ashraf W. Khir, John R. Cockcroft, Ian B. Wilkinson, Kevin M. O’Shaughnessy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f4f9722e6a394997bed126349eb17c39
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spelling	oai:doaj.org-article:f4f9722e6a394997bed126349eb17c392021-12-02T15:09:10ZThe matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness10.1038/s41598-018-25851-52045-2322https://doaj.org/article/f4f9722e6a394997bed126349eb17c392018-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25851-5https://doaj.org/toc/2045-2322Abstract Stiffening of the aorta is an important independent risk factor for myocardial infarction and stroke. Yet its genetics is complex and little is known about its molecular drivers. We have identified for the first time, tagSNPs in the genes for extracellular matrix proteins, aggrecan and fibulin-1, that modulate stiffness in young healthy adults. We confirmed SNP associations with ex vivo stiffness measurements and expression studies in human donor aortic tissues. Both aggrecan and fibulin-1 were found in the aortic wall, but with marked differences in the distribution and glycosylation of aggrecan reflecting loss of chondroitin-sulphate binding domains. These differences were age-dependent but the striking finding was the acceleration of this process in stiff versus elastic young aortas. These findings suggest that aggrecan and fibulin-1 have critical roles in determining the biomechanics of the aorta and their modification with age could underpin age-related aortic stiffening.YasminRaya Al MaskariCarmel M. McEnierySarah E. ClearyYe LiKeith SiewNichola L. FiggAshraf W. KhirJohn R. CockcroftIan B. WilkinsonKevin M. O’ShaughnessyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-16 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yasmin Raya Al Maskari Carmel M. McEniery Sarah E. Cleary Ye Li Keith Siew Nichola L. Figg Ashraf W. Khir John R. Cockcroft Ian B. Wilkinson Kevin M. O’Shaughnessy The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness
description	Abstract Stiffening of the aorta is an important independent risk factor for myocardial infarction and stroke. Yet its genetics is complex and little is known about its molecular drivers. We have identified for the first time, tagSNPs in the genes for extracellular matrix proteins, aggrecan and fibulin-1, that modulate stiffness in young healthy adults. We confirmed SNP associations with ex vivo stiffness measurements and expression studies in human donor aortic tissues. Both aggrecan and fibulin-1 were found in the aortic wall, but with marked differences in the distribution and glycosylation of aggrecan reflecting loss of chondroitin-sulphate binding domains. These differences were age-dependent but the striking finding was the acceleration of this process in stiff versus elastic young aortas. These findings suggest that aggrecan and fibulin-1 have critical roles in determining the biomechanics of the aorta and their modification with age could underpin age-related aortic stiffening.
format	article
author	Yasmin Raya Al Maskari Carmel M. McEniery Sarah E. Cleary Ye Li Keith Siew Nichola L. Figg Ashraf W. Khir John R. Cockcroft Ian B. Wilkinson Kevin M. O’Shaughnessy
author_facet	Yasmin Raya Al Maskari Carmel M. McEniery Sarah E. Cleary Ye Li Keith Siew Nichola L. Figg Ashraf W. Khir John R. Cockcroft Ian B. Wilkinson Kevin M. O’Shaughnessy
author_sort	Yasmin
title	The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness
title_short	The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness
title_full	The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness
title_fullStr	The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness
title_full_unstemmed	The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness
title_sort	matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/f4f9722e6a394997bed126349eb17c39
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The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness

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