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

Published version
Peer-reviewed

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Authors

McEniery, Carmel M 
Cleary, Sarah E 
Li, Ye 

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.

Description

Keywords

Adolescent, Adult, Aggrecans, Aging, Aorta, Calcium-Binding Proteins, Female, Humans, Male, Polymorphism, Single Nucleotide, Vascular Stiffness

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

8

Publisher

Springer Science and Business Media LLC
Sponsorship
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (None)