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

Yasmin, ; Al Maskari, R; McEniery, CM; Cleary, SE; Li, Y; Siew, K; Figg, NL; ... O'Shaughnessy, KM; + view all (2018) The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness. Scientific Reports , 8 , Article 8550. 10.1038/s41598-018-25851-5. Green open access

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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.

Type: Article
Title: The matrix proteins aggrecan and fibulin-1 play a key role in determining aortic stiffness
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-018-25851-5
Publisher version: http://dx.doi.org/10.1038/s41598-018-25851-5
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Internal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10089759
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