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COMP (Cartilage Oligomeric Matrix Protein) Neoepitope A Novel Biomarker to Identify Symptomatic Carotid Stenosis

Sandstedt, Joakim and Vargmar, Karin and Bjorkman, Kristina and Ruetschi, Ulla and Bergstrom, Goran and Hulten, Lillemor Mattsson and Skiöldebrand, Eva (2021). COMP (Cartilage Oligomeric Matrix Protein) Neoepitope A Novel Biomarker to Identify Symptomatic Carotid Stenosis. Arteriosclerosis, thrombosis, and vascular biology. 41 , 1218-1228
[Research article]

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Abstract

Objective:COMP (cartilage oligomeric matrix protein) is abundantly expressed in the cardiovascular system, cartilage, and atherosclerotic plaques. We investigated if the total COMP (COMPtotal) and COMP neoepitope (COMPneo) with other cardiovascular markers and clinical parameters could identify symptomatic carotid stenosis.Approach and Results:Blood samples were collected from patients with symptomatic carotid stenosis (stenosis, n=50), patients with stroke without carotid stenosis but small plaques (plaque, n=50), and control subjects (n=50). COMPtotal and COMPneo were measured using an ELISA. Ninety-two cardiovascular disease markers were measured by the Olink CVD kit. The presence of native COMP and COMPneo was determined by immunohistochemistry. The concentration of COMPneo was higher and COMPtotal was lower in the stenosis group. When the concentration was compared between the stenosis and control groups, IL-1ra (interleukin-1 receptor antagonist protein), IL6 (interleukin-6), REN (Renin), MMP1 (matrix metalloproteinase-1), TRAIL-R2 (tumor necrosis factor-related apoptosis-inducing ligand receptor 2), ITGB1BP2 (integrin beta 1 binding protein 2), and COMPneo were predictive of stenosis. Conversely, KLK6 (kallikrein-6), COMPtotal, NEMO (nuclear factor-kappa-B essential modulator), SRC (Proto-oncogene tyrosine-protein kinase Src), SIRT2 (SIR2-like protein), CD40 (cluster of differentiation 40), TF (tissue factor), MP (myoglobin), and RAGE (receptor for advanced glycation end-products) were predictive of the control group. Model reproducibility was good with the receiver operating characteristic plot area under the curve being 0.86. When comparing the plaque group and stenosis group, COMPneo, GAL (galanin), and PTX3 (pentraxin-related protein PTX3) were predictive of stenosis. Model reproducibility was excellent (receiver operating characteristic plot area under the curve 0.92). COMPneo was detected in smooth muscle-, endothelial-, and foam-cells in carotid stenosis.Conclusions:Degradation of COMP may be associated with atherosclerosis progression and generation of a specific COMP fragment-COMPneo. This may represent a novel biomarker that together with COMPtotal and other risk-markers could be used to identify symptomatic carotid stenosis.

Authors/Creators:Sandstedt, Joakim and Vargmar, Karin and Bjorkman, Kristina and Ruetschi, Ulla and Bergstrom, Goran and Hulten, Lillemor Mattsson and Skiöldebrand, Eva
Title:COMP (Cartilage Oligomeric Matrix Protein) Neoepitope A Novel Biomarker to Identify Symptomatic Carotid Stenosis
Series Name/Journal:Arteriosclerosis, thrombosis, and vascular biology
Year of publishing :2021
Volume:41
Page range:1218-1228
Number of Pages:11
Publisher:LIPPINCOTT WILLIAMS AND WILKINS
ISSN:1079-5642
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 302 Clinical Medicine > Cardiac and Cardiovascular Systems
Keywords:atherosclerosis, biomarker, carotid stenosis, extracellular matrix proteins, plasma, stroke
URN:NBN:urn:nbn:se:slu:epsilon-p-112160
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-112160
Additional ID:
Type of IDID
DOI10.1161/ATVBAHA.120.314720
Web of Science (WoS)000639315600024
ID Code:24519
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Department of Biomedical Science and Veterinary Public Health
Deposited By: SLUpub Connector
Deposited On:11 Jun 2021 12:02
Metadata Last Modified:11 Jun 2021 12:11

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