Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization

Susanne Wagner,1 J&ouml;rg Schnorr,1 Antje Ludwig,2 Verena Stangl,2 Monika Ebert,1 Bernd Hamm,1 Matthias Taupitz11Department of Radiology, Section of Experimental Radiology, Charit&eacute; &ndash; Universit&auml;tsmedizin Berlin, Campus Charit&eacute; Mitte, a...

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Autores principales:	Wagner S, Schnorr J, Ludwig A, Stangl V, Ebert M, Hamm B, Taupitz M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/de3473874f97449690567882f9149259
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spelling	oai:doaj.org-article:de3473874f97449690567882f91492592021-12-02T05:07:53ZContrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization1176-91141178-2013https://doaj.org/article/de3473874f97449690567882f91492592013-02-01T00:00:00Zhttp://www.dovepress.com/contrast-enhanced-mr-imaging-of-atherosclerosis-using-citrate-coated-s-a12256https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Susanne Wagner,1 J&ouml;rg Schnorr,1 Antje Ludwig,2 Verena Stangl,2 Monika Ebert,1 Bernd Hamm,1 Matthias Taupitz11Department of Radiology, Section of Experimental Radiology, Charit&eacute; &ndash; Universit&auml;tsmedizin Berlin, Campus Charit&eacute; Mitte, and Campus Benjamin Franklin, Berlin, Germany; 2Department of Cardiology, Section of Experimental Cardiology, Charit&eacute; &ndash; Universit&auml;tsmedizin Berlin, Campus Charit&eacute; Mitte, Berlin, GermanyObjective: To evaluate the suitability of citrate-coated very small superparamagnetic iron oxide particles (VSOP) as a contrast agent for identifying inflammation in atherosclerotic lesions using magnetic resonance imaging (MRI).Methods and results: VSOP, which have already been evaluated as a blood pool contrast agent for MR angiography in human clinical trials, were investigated in Watanabe heritable hyperlipidemic rabbits to determine to what extent their accumulation in atherosclerotic lesions is a function of macrophage density and other characteristics of progressive atherosclerotic plaques. In advanced atherosclerotic lesions, a significant MRI signal loss was found within 1 hour after intravenous administration of VSOP at the intended clinical dose of 0.05 mmol Fe/kg. Histological examinations confirmed correlations between the loss of MRI signal in the vessel wall and the presence of Prussian blue-stained iron colocalized with macrophages in the plaque cap, but surprisingly also with calcifying microvesicles at the intimomedial interface. Critical electrolyte magnesium chloride concentration in combination with Alcian blue stain indicates that highly sulfated glycosaminoglycans are a major constituent of these calcifying microvesicles, which may serve as the key molecules for binding VSOP due to their highly complexing properties.Conclusion: Calcifying microvesicles and macrophages are the targets for intravenously injected VSOP in atherosclerotic plaques, suggesting that VSOP-enhanced MRI may render clinically relevant information on the composition and inflammatory activity of progressive atherosclerotic lesions at risk of destabilization.Keywords: atherosclerosis, inflammation, magnetic resonance imaging, iron oxide nanoparticles, glycosaminoglycans, calcifying microvesiclesWagner SSchnorr JLudwig AStangl VEbert MHamm BTaupitz MDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 767-779 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Wagner S Schnorr J Ludwig A Stangl V Ebert M Hamm B Taupitz M Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization
description	Susanne Wagner,1 J&ouml;rg Schnorr,1 Antje Ludwig,2 Verena Stangl,2 Monika Ebert,1 Bernd Hamm,1 Matthias Taupitz11Department of Radiology, Section of Experimental Radiology, Charit&eacute; &ndash; Universit&auml;tsmedizin Berlin, Campus Charit&eacute; Mitte, and Campus Benjamin Franklin, Berlin, Germany; 2Department of Cardiology, Section of Experimental Cardiology, Charit&eacute; &ndash; Universit&auml;tsmedizin Berlin, Campus Charit&eacute; Mitte, Berlin, GermanyObjective: To evaluate the suitability of citrate-coated very small superparamagnetic iron oxide particles (VSOP) as a contrast agent for identifying inflammation in atherosclerotic lesions using magnetic resonance imaging (MRI).Methods and results: VSOP, which have already been evaluated as a blood pool contrast agent for MR angiography in human clinical trials, were investigated in Watanabe heritable hyperlipidemic rabbits to determine to what extent their accumulation in atherosclerotic lesions is a function of macrophage density and other characteristics of progressive atherosclerotic plaques. In advanced atherosclerotic lesions, a significant MRI signal loss was found within 1 hour after intravenous administration of VSOP at the intended clinical dose of 0.05 mmol Fe/kg. Histological examinations confirmed correlations between the loss of MRI signal in the vessel wall and the presence of Prussian blue-stained iron colocalized with macrophages in the plaque cap, but surprisingly also with calcifying microvesicles at the intimomedial interface. Critical electrolyte magnesium chloride concentration in combination with Alcian blue stain indicates that highly sulfated glycosaminoglycans are a major constituent of these calcifying microvesicles, which may serve as the key molecules for binding VSOP due to their highly complexing properties.Conclusion: Calcifying microvesicles and macrophages are the targets for intravenously injected VSOP in atherosclerotic plaques, suggesting that VSOP-enhanced MRI may render clinically relevant information on the composition and inflammatory activity of progressive atherosclerotic lesions at risk of destabilization.Keywords: atherosclerosis, inflammation, magnetic resonance imaging, iron oxide nanoparticles, glycosaminoglycans, calcifying microvesicles
format	article
author	Wagner S Schnorr J Ludwig A Stangl V Ebert M Hamm B Taupitz M
author_facet	Wagner S Schnorr J Ludwig A Stangl V Ebert M Hamm B Taupitz M
author_sort	Wagner S
title	Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization
title_short	Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization
title_full	Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization
title_fullStr	Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization
title_full_unstemmed	Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization
title_sort	contrast-enhanced mr imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/de3473874f97449690567882f9149259
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Contrast-enhanced MR imaging of atherosclerosis using citrate-coated superparamagnetic iron oxide nanoparticles: calcifying microvesicles as imaging target for plaque characterization

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