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Extracellular matrix proteomics identifies molecular signature of atherosclerotic plaques from symptomatic patients

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Title: Extracellular matrix proteomics identifies molecular signature of atherosclerotic plaques from symptomatic patients
Authors: Langley, S
Willeit, K
Didangelos, A
Perisic Matic, L
Skroblin, P
Barallobre-Barreiro, J
Lengquist, M
Rungger, G
Kapustin, A
Kedenko, L
Molenaar, C
Lu, R
Barwari, T
Suna, G
Yin, X
Iglseder, B
Paulweber, B
Willeit, P
Shalhoub, J
Pasterkamp, G
Davies, AH
Monaco, C
Hedin, U
Shanahan, C
Willeit, J
Kiechl, S
Mayr, M
Item Type: Journal Article
Abstract: Recent findings have challenged the prevailing histology- or imaging-based definition of the “vulnerable plaque”. To investigate molecular characteristics associated with “clinical instability” of atherosclerosis, we performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from symptomatic versus asymptomatic patients. The proteomics data were integrated with gene expression profiling and an analysis of protein secretion by lipid-loaded human vascular smooth muscle cells. The molecular signature of plaques from symptomatic patients identified by proteomics and at least one of the other two approaches comprised matrix metalloproteinase-9, chitinase-3- like protein 1, S100 calcium binding protein A8, S100 calcium binding protein A9, cathepsin B, fibronectin and galectin-3-binding protein. Biomarker candidates were measured in 685 subjects of the Bruneck Study and found to be significantly associated with the progression to advanced atherosclerosis (as assessed by repeated carotid ultrasound) and the incidence of cardiovascular disease over a 10-year followup period. A 4-biomarker signature (matrix metalloproteinase-9, S100A8/S100A9, cathepsin D, and galectin-3-binding protein) improved risk prediction in terms of risk discrimination and classification and was successfully replicated in a second independent population (SAPHIR Study). Our study highlights the strength of tissuebased proteomics for biomarker discovery.
Issue Date: 3-Apr-2017
Date of Acceptance: 19-Jan-2017
URI: http://hdl.handle.net/10044/1/45025
DOI: https://dx.doi.org/10.1172/JCI86924
ISSN: 1558-8238
Publisher: American Society for Clinical Investigation
Start Page: 1546
End Page: 1560
Journal / Book Title: Journal of Clinical Investigation
Volume: 127
Issue: 4
Copyright Statement: © 2017 Langley et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Imperial College Trust
Graham-Dixon Charitable Trust
The Circulation Foundation
Funder's Grant Number: N/A
DKCC_P09393
Mary Davies F'Ship
Keywords: Immunology
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



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