Abstract
To date, no plaque-derived blood biomarker is available to allow diagnosis, prognosis or monitoring of atherosclerotic vascular diseases. In this study, specimens of thrombendarterectomy material from carotid and iliac arteries were incubated in protein-free medium to obtain plaque and control secretomes for subsequent subtractive phage display. The selection of nine plaque secretome-specific antibodies and the analysis of their immunopurified antigens by mass spectrometry led to the identification of 22 proteins. One of them, junction plakoglobin (JUP-81) and its smaller isoforms (referred to as JUP-63, JUP-55 and JUP-30 by molecular weight) were confirmed by immunohistochemistry and immunoblotting with independent antibodies to be present in atherosclerotic plaques and their secretomes, coronary thrombi of patients with acute coronary syndrome (ACS) and macrophages differentiated from peripheral blood monocytes as well as macrophage-like cells differentiated from THP1 cells. Plasma of patients with stable coronary artery disease (CAD) (n = 15) and ACS (n = 11) contained JUP-81 at more than 2- and 14-fold higher median concentrations, respectively, than plasma of CAD-free individuals (n = 13). In conclusion, this proof of principle study identified and verified JUP isoforms as potential plasma biomarkers for atherosclerosis. Clinical validation studies are needed to determine its diagnostic efficacy and clinical utility as a biomarker for diagnosis, prognosis or monitoring of atherosclerotic vascular diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Coronary Syndrome / blood
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Acute Coronary Syndrome / metabolism
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Aged
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Amino Acid Sequence
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Antibodies / genetics
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Antibodies / metabolism*
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Atherosclerosis / diagnosis
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Atherosclerosis / metabolism*
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Biomarkers / blood
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Biomarkers / metabolism*
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Carotid Arteries / metabolism
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Carotid Arteries / pathology
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Carotid Arteries / surgery
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Cell Line
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Coronary Artery Disease / blood
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Coronary Artery Disease / metabolism
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Desmoplakins / genetics
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Desmoplakins / immunology
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Desmoplakins / metabolism*
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Endarterectomy
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Humans
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Iliac Artery / metabolism
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Iliac Artery / pathology
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Iliac Artery / surgery
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Immunoblotting
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Immunohistochemistry
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Macrophages / metabolism
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Macrophages / pathology
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Male
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Mass Spectrometry
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Middle Aged
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Molecular Sequence Data
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Peptide Library
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Plaque, Atherosclerotic / blood
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Plaque, Atherosclerotic / metabolism
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Protein Isoforms / genetics
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Protein Isoforms / immunology
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Protein Isoforms / metabolism
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Proteomics / methods
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Sequence Homology, Amino Acid
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gamma Catenin
Substances
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Antibodies
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Biomarkers
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Desmoplakins
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JUP protein, human
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Peptide Library
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Protein Isoforms
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gamma Catenin
Grants and funding
This work was financially supported by a joint grant from the Zurich Center for Integrative Human Physiology (ZIHP) (
www.zihp.uzh.ch), by a grant from the Olga Mayenfisch Foundation, by the Hartmann Mueller Foundation (
www.hms.uzh.ch), the Walter L. & Johanna Wolf Foundation, the Swiss Heart Foundation (
www.swissheart.ch) and the Swiss National Science Foundation (
www.snf.ch) (SPUM – Special Program University Medicine, ACS inflammation) (
www.spum-acs.ch). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.