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

被引：34

作者：

Yasmin ^{[1
]}

Al Maskari, Raya ^{[1
]}

McEniery, Carmel M. ^{[1
]}

Cleary, Sarah E. ^{[1
]}

Li, Ye ^{[2
]}

Siew, Keith ^{[1
]}

Figg, Nichola L. ^{[3
]}

Khir, Ashraf W. ^{[2
]}

Cockcroft, John R. ^{[4
]}

Wilkinson, Ian B. ^{[1
]}

O'Shaughnessy, Kevin M. ^{[1
]}

机构：

[1] Univ Cambridge, Addenbrookes Hosp, Div Expt Med Immunotherapeut, Cambridge, England

[2] Brunel Univ, Brunel Inst Bioengn, Uxbridge, Middx, England

[3] Univ Cambridge, Addenbrookes Hosp, Div Cardiovasc Med, Cambridge, England

[4] Columbia Univ, New York Presbyterian Hosp, Div Cardiol, New York, NY USA

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

PULSE-WAVE VELOCITY; GENOME-WIDE ASSOCIATION; AGE-RELATED-CHANGES; ARTERIAL STIFFNESS; PLASMA FIBULIN-1; CORE PROTEIN; DISEASE; GENES; PATHOPHYSIOLOGY; EXPRESSION;

D O I：

10.1038/s41598-018-25851-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：16

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