Antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.

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 secre...

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Autores principales: Seraina Cooksley-Decasper, Hans Reiser, Daniela S Thommen, Barbara Biedermann, Michel Neidhart, Joanna Gawinecka, Gieri Cathomas, Fabian C Franzeck, Christophe Wyss, Roland Klingenberg, Paolo Nanni, Bernd Roschitzki, Christian Matter, Petra Wolint, Maximilian Y Emmert, Marc Husmann, Beatrice Amann-Vesti, Wilibald Maier, Steffen Gay, Thomas F Lüscher, Arnold von Eckardstein, Danielle Hof
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:bb51be72e980485c9302e17808f891b82021-11-18T08:11:18ZAntibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.1932-620310.1371/journal.pone.0047985https://doaj.org/article/bb51be72e980485c9302e17808f891b82012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23110151/?tool=EBIhttps://doaj.org/toc/1932-6203To 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.Seraina Cooksley-DecasperHans ReiserDaniela S ThommenBarbara BiedermannMichel NeidhartJoanna GawineckaGieri CathomasFabian C FranzeckChristophe WyssRoland KlingenbergPaolo NanniBernd RoschitzkiChristian MatterPetra WolintMaximilian Y EmmertMarc HusmannBeatrice Amann-VestiWilibald MaierSteffen GayThomas F LüscherArnold von EckardsteinDanielle HofPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e47985 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Seraina Cooksley-Decasper
Hans Reiser
Daniela S Thommen
Barbara Biedermann
Michel Neidhart
Joanna Gawinecka
Gieri Cathomas
Fabian C Franzeck
Christophe Wyss
Roland Klingenberg
Paolo Nanni
Bernd Roschitzki
Christian Matter
Petra Wolint
Maximilian Y Emmert
Marc Husmann
Beatrice Amann-Vesti
Wilibald Maier
Steffen Gay
Thomas F Lüscher
Arnold von Eckardstein
Danielle Hof
Antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.
description 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.
format article
author Seraina Cooksley-Decasper
Hans Reiser
Daniela S Thommen
Barbara Biedermann
Michel Neidhart
Joanna Gawinecka
Gieri Cathomas
Fabian C Franzeck
Christophe Wyss
Roland Klingenberg
Paolo Nanni
Bernd Roschitzki
Christian Matter
Petra Wolint
Maximilian Y Emmert
Marc Husmann
Beatrice Amann-Vesti
Wilibald Maier
Steffen Gay
Thomas F Lüscher
Arnold von Eckardstein
Danielle Hof
author_facet Seraina Cooksley-Decasper
Hans Reiser
Daniela S Thommen
Barbara Biedermann
Michel Neidhart
Joanna Gawinecka
Gieri Cathomas
Fabian C Franzeck
Christophe Wyss
Roland Klingenberg
Paolo Nanni
Bernd Roschitzki
Christian Matter
Petra Wolint
Maximilian Y Emmert
Marc Husmann
Beatrice Amann-Vesti
Wilibald Maier
Steffen Gay
Thomas F Lüscher
Arnold von Eckardstein
Danielle Hof
author_sort Seraina Cooksley-Decasper
title Antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.
title_short Antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.
title_full Antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.
title_fullStr Antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.
title_full_unstemmed Antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.
title_sort antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/bb51be72e980485c9302e17808f891b8
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