AustralieFrV1, Main, Exploration, bibRecord, 005347

In Vivo Detection of Activated Platelets Allows Characterizing Rupture of Atherosclerotic Plaques with Molecular Magnetic Resonance Imaging in Mice

Identifieur interne : 005347 ( Main/Exploration ); précédent : 005346; suivant : 005348

In Vivo Detection of Activated Platelets Allows Characterizing Rupture of Atherosclerotic Plaques with Molecular Magnetic Resonance Imaging in Mice

Auteurs : Dominik Von Elverfeldt [Allemagne] ; Constantin Von Zur Muhlen [Allemagne] ; Kristina Wiens [Allemagne] ; Irene Neudorfer [Allemagne] ; Andreas Zirlik [Allemagne] ; Mirko Meissner [Allemagne] ; Peg Tilly [France] ; Anne-Laure Charles [France] ; Christoph Bode [Allemagne] ; Karlheinz Peter [Australie] ; Jean-Etienne Fabre [France]

Source :

PLoS ONE [ 1932-6203 ] ; 2012.

RBID : PMC:3441740

Abstract

Background

Early and non-invasive detection of platelets on micro atherothrombosis provides a means to identify unstable plaque and thereby allowing prophylactic treatment towards prevention of stroke or myocardial infarction. Molecular magnetic resonance imaging (mMRI) of activated platelets as early markers of plaque rupture using targeted contrast agents is a promising strategy. In this study, we aim to specifically image activated platelets in murine atherothrombosis by in vivo mMRI, using a dedicated animal model of plaque rupture.

Methods

An antibody targeting ligand-induced binding sites (LIBS) on the glycoprotein IIb/IIIa-receptor of activated platelets was conjugated to microparticles of iron oxide (MPIO) to form the LIBS-MPIO contrast agent causing a signal-extinction in T2*-weighted MRI. ApoE^−/− mice (60 weeks-old) were fed a high fat diet for 5 weeks. Using a small needle, the surface of their carotid plaques was scratched under blood flow to induce atherothrombosis. In vivo 9.4 Tesla MRI was performed before and repetitively after intravenous injection of either LIBS-MPIO versus non-targeted-MPIO.

Results

LIBS-MPIO injected animals showed a significant signal extinction (p<0.05) in MRI, corresponding to the site of plaque rupture and atherothrombosis in histology. The signal attenuation was effective for atherothrombosis occupying ≥2% of the vascular lumen. Histology further confirmed significant binding of LIBS-MPIO compared to control-MPIO on the thrombus developing on the surface of ruptured plaques (p<0.01).

Conclusion

in vivo mMRI detected activated platelets on mechanically ruptured atherosclerotic plaques in ApoE^−/− mice with a high sensititvity. This imaging technology represents a unique opportunity for noninvasive detection of atherothrombosis and the identification of unstable atherosclerotic plaques with the ultimate promise to prevent strokes and myocardial infarctions.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441740

DOI: 10.1371/journal.pone.0045008
PubMed: 23028736
PubMed Central: 3441740

Affiliations:

Le document en format XML

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<author><name sortKey="Neudorfer, Irene" sort="Neudorfer, Irene" uniqKey="Neudorfer I" first="Irene" last="Neudorfer">Irene Neudorfer</name>
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<author><name sortKey="Zirlik, Andreas" sort="Zirlik, Andreas" uniqKey="Zirlik A" first="Andreas" last="Zirlik">Andreas Zirlik</name>
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<author><name sortKey="Meissner, Mirko" sort="Meissner, Mirko" uniqKey="Meissner M" first="Mirko" last="Meissner">Mirko Meissner</name>
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<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Tilly, Peg" sort="Tilly, Peg" uniqKey="Tilly P" first="Peg" last="Tilly">Peg Tilly</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 7104/Université de Strasbourg, Illkirch</wicri:regionArea>
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<author><name sortKey="Charles, Anne Laure" sort="Charles, Anne Laure" uniqKey="Charles A" first="Anne-Laure" last="Charles">Anne-Laure Charles</name>
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<author><name sortKey="Bode, Christoph" sort="Bode, Christoph" uniqKey="Bode C" first="Christoph" last="Bode">Christoph Bode</name>
<affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Department of Cardiology and Angiology I, University Heart Center, Freiburg, Germany</addr-line>
</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Cardiology and Angiology I, University Heart Center, Freiburg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Fribourg-en-Brisgau</region>
<settlement type="city">Fribourg-en-Brisgau</settlement>
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<author><name sortKey="Peter, Karlheinz" sort="Peter, Karlheinz" uniqKey="Peter K" first="Karlheinz" last="Peter">Karlheinz Peter</name>
<affiliation wicri:level="3"><nlm:aff id="aff4"><addr-line>Baker IDI Heart & Diabetes Institute, Melbourne, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Baker IDI Heart & Diabetes Institute, Melbourne</wicri:regionArea>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fabre, Jean Etienne" sort="Fabre, Jean Etienne" uniqKey="Fabre J" first="Jean-Etienne" last="Fabre">Jean-Etienne Fabre</name>
<affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 7104/Université de Strasbourg, Illkirch, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de Santé et de Recherche Médicale (INSERM) U964/Centre National de Recherche Scientifique (CNRS) UMR 7104/Université de Strasbourg, Illkirch</wicri:regionArea>
<wicri:noRegion>Illkirch</wicri:noRegion>
<orgName type="university">Université de Strasbourg</orgName>
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<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2012">2012</date>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Early and non-invasive detection of platelets on micro atherothrombosis provides a means to identify unstable plaque and thereby allowing prophylactic treatment towards prevention of stroke or myocardial infarction. Molecular magnetic resonance imaging (mMRI) of activated platelets as early markers of plaque rupture using targeted contrast agents is a promising strategy. In this study, we aim to specifically image activated platelets in murine atherothrombosis by <italic>in vivo</italic>
 mMRI, using a dedicated animal model of plaque rupture.</p>
</sec>
<sec><title>Methods</title>
<p>An antibody targeting ligand-induced binding sites (LIBS) on the glycoprotein IIb/IIIa-receptor of activated platelets was conjugated to microparticles of iron oxide (MPIO) to form the LIBS-MPIO contrast agent causing a signal-extinction in T2*-weighted MRI. <italic>ApoE<sup>−/−</sup>
</italic>
 mice (60 weeks-old) were fed a high fat diet for 5 weeks. Using a small needle, the surface of their carotid plaques was scratched under blood flow to induce atherothrombosis. <italic>In vivo</italic>
 9.4 Tesla MRI was performed before and repetitively after intravenous injection of either LIBS-MPIO versus non-targeted-MPIO.</p>
</sec>
<sec><title>Results</title>
<p>LIBS-MPIO injected animals showed a significant signal extinction (p<0.05) in MRI, corresponding to the site of plaque rupture and atherothrombosis in histology. The signal attenuation was effective for atherothrombosis occupying ≥2% of the vascular lumen. Histology further confirmed significant binding of LIBS-MPIO compared to control-MPIO on the thrombus developing on the surface of ruptured plaques (p<0.01).</p>
</sec>
<sec><title>Conclusion</title>
<p><italic>in vivo</italic>
 mMRI detected activated platelets on mechanically ruptured atherosclerotic plaques in ApoE<sup>−/−</sup>
 mice with a high sensititvity. This imaging technology represents a unique opportunity for noninvasive detection of atherothrombosis and the identification of unstable atherosclerotic plaques with the ultimate promise to prevent strokes and myocardial infarctions.</p>
</sec>
</div>
</front>
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</div1>
</back>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>France</li>
</country>
<region><li>Alsace (région administrative)</li>
<li>Bade-Wurtemberg</li>
<li>District de Fribourg-en-Brisgau</li>
<li>Grand Est</li>
<li>Victoria (État)</li>
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<settlement><li>Fribourg-en-Brisgau</li>
<li>Melbourne</li>
<li>Strasbourg</li>
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<orgName><li>Université de Strasbourg</li>
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</list>
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<name sortKey="Bode, Christoph" sort="Bode, Christoph" uniqKey="Bode C" first="Christoph" last="Bode">Christoph Bode</name>
<name sortKey="Meissner, Mirko" sort="Meissner, Mirko" uniqKey="Meissner M" first="Mirko" last="Meissner">Mirko Meissner</name>
<name sortKey="Neudorfer, Irene" sort="Neudorfer, Irene" uniqKey="Neudorfer I" first="Irene" last="Neudorfer">Irene Neudorfer</name>
<name sortKey="Von Zur Muhlen, Constantin" sort="Von Zur Muhlen, Constantin" uniqKey="Von Zur Muhlen C" first="Constantin" last="Von Zur Muhlen">Constantin Von Zur Muhlen</name>
<name sortKey="Wiens, Kristina" sort="Wiens, Kristina" uniqKey="Wiens K" first="Kristina" last="Wiens">Kristina Wiens</name>
<name sortKey="Zirlik, Andreas" sort="Zirlik, Andreas" uniqKey="Zirlik A" first="Andreas" last="Zirlik">Andreas Zirlik</name>
</country>
<country name="France"><region name="Grand Est"><name sortKey="Tilly, Peg" sort="Tilly, Peg" uniqKey="Tilly P" first="Peg" last="Tilly">Peg Tilly</name>
</region>
<name sortKey="Charles, Anne Laure" sort="Charles, Anne Laure" uniqKey="Charles A" first="Anne-Laure" last="Charles">Anne-Laure Charles</name>
<name sortKey="Fabre, Jean Etienne" sort="Fabre, Jean Etienne" uniqKey="Fabre J" first="Jean-Etienne" last="Fabre">Jean-Etienne Fabre</name>
</country>
<country name="Australie"><region name="Victoria (État)"><name sortKey="Peter, Karlheinz" sort="Peter, Karlheinz" uniqKey="Peter K" first="Karlheinz" last="Peter">Karlheinz Peter</name>
</region>
</country>
</tree>
</affiliations>
</record>

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In Vivo Detection of Activated Platelets Allows Characterizing Rupture of Atherosclerotic Plaques with Molecular Magnetic Resonance Imaging in Mice

In Vivo Detection of Activated Platelets Allows Characterizing Rupture of Atherosclerotic Plaques with Molecular Magnetic Resonance Imaging in Mice

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