Ex Vivo and in Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac Fibrosis

Cardiac fibrosis is a major hallmark of cardiac diseases. For evaluation of cardiac fibrosis, the development of highly specific and preferably noninvasive methods is desired. Our aim was to evaluate CNA35, a protein known to specifically bind to collagen, as a specific marker of cardiac fibrosis. F...

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Main Authors: Sanne de Jong, Lars B. van Middendorp, Robin H.A. Hermans, Jacques M.T. de Bakker, Marti F.A. Bierhuizen, Frits W. Prinzen, Harold V.M. van Rijen, Mario Losen, Marc A. Vos, Marc A.M.J. van Zandvoort
Format: Article
Language:English
Published: SAGE Publishing 2014-12-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2014.00036
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author Sanne de Jong
Lars B. van Middendorp
Robin H.A. Hermans
Jacques M.T. de Bakker
Marti F.A. Bierhuizen
Frits W. Prinzen
Harold V.M. van Rijen
Mario Losen
Marc A. Vos
Marc A.M.J. van Zandvoort
author_facet Sanne de Jong
Lars B. van Middendorp
Robin H.A. Hermans
Jacques M.T. de Bakker
Marti F.A. Bierhuizen
Frits W. Prinzen
Harold V.M. van Rijen
Mario Losen
Marc A. Vos
Marc A.M.J. van Zandvoort
author_sort Sanne de Jong
collection DOAJ
description Cardiac fibrosis is a major hallmark of cardiac diseases. For evaluation of cardiac fibrosis, the development of highly specific and preferably noninvasive methods is desired. Our aim was to evaluate CNA35, a protein known to specifically bind to collagen, as a specific marker of cardiac fibrosis. Fluorescently labeled CNA35 was applied ex vivo on tissue sections of fibrotic rat, mouse, and canine myocardium. After quantification of CNA35, sections were examined with picrosirius red (PSR) and compared to CNA35. Furthermore, fluorescently labeled CNA35 was administered in vivo in mice. Hearts were isolated, and CNA35 labeling was examined in tissue sections. Serial sections were histologically examined with PSR. Ex vivo application of CNA35 showed specific binding to collagen and a high correlation with PSR (Pearson r = .86 for mice/rats and r = .98 for canine; both p < .001). After in vivo administration, CNA35 labeling was observed around individual cardiomyocytes, indicating its ability to penetrate cardiac endothelium. High correlation was observed between CNA35 and PSR ( r = .91, p < .001). CNA35 specifically binds to cardiac collagen and can cross the endothelial barrier. Therefore, labeled CNA35 is useful to specifically detect collagen both ex vivo and in vivo and potentially can be converted to a noninvasive method to detect cardiac fibrosis.
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spelling doaj-art-a55eeeac91b44310b10638cc145d151f2025-08-20T02:44:43ZengSAGE PublishingMolecular Imaging1536-01212014-12-011310.2310/7290.2014.0003610.2310_7290.2014.00036Ex Vivo and in Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac FibrosisSanne de JongLars B. van MiddendorpRobin H.A. HermansJacques M.T. de BakkerMarti F.A. BierhuizenFrits W. PrinzenHarold V.M. van RijenMario LosenMarc A. VosMarc A.M.J. van ZandvoortCardiac fibrosis is a major hallmark of cardiac diseases. For evaluation of cardiac fibrosis, the development of highly specific and preferably noninvasive methods is desired. Our aim was to evaluate CNA35, a protein known to specifically bind to collagen, as a specific marker of cardiac fibrosis. Fluorescently labeled CNA35 was applied ex vivo on tissue sections of fibrotic rat, mouse, and canine myocardium. After quantification of CNA35, sections were examined with picrosirius red (PSR) and compared to CNA35. Furthermore, fluorescently labeled CNA35 was administered in vivo in mice. Hearts were isolated, and CNA35 labeling was examined in tissue sections. Serial sections were histologically examined with PSR. Ex vivo application of CNA35 showed specific binding to collagen and a high correlation with PSR (Pearson r = .86 for mice/rats and r = .98 for canine; both p < .001). After in vivo administration, CNA35 labeling was observed around individual cardiomyocytes, indicating its ability to penetrate cardiac endothelium. High correlation was observed between CNA35 and PSR ( r = .91, p < .001). CNA35 specifically binds to cardiac collagen and can cross the endothelial barrier. Therefore, labeled CNA35 is useful to specifically detect collagen both ex vivo and in vivo and potentially can be converted to a noninvasive method to detect cardiac fibrosis.https://doi.org/10.2310/7290.2014.00036
spellingShingle Sanne de Jong
Lars B. van Middendorp
Robin H.A. Hermans
Jacques M.T. de Bakker
Marti F.A. Bierhuizen
Frits W. Prinzen
Harold V.M. van Rijen
Mario Losen
Marc A. Vos
Marc A.M.J. van Zandvoort
Ex Vivo and in Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac Fibrosis
Molecular Imaging
title Ex Vivo and in Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac Fibrosis
title_full Ex Vivo and in Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac Fibrosis
title_fullStr Ex Vivo and in Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac Fibrosis
title_full_unstemmed Ex Vivo and in Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac Fibrosis
title_short Ex Vivo and in Vivo Administration of Fluorescent CNA35 Specifically Marks Cardiac Fibrosis
title_sort ex vivo and in vivo administration of fluorescent cna35 specifically marks cardiac fibrosis
url https://doi.org/10.2310/7290.2014.00036
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