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EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction

Inhibition of extracellular matrix (ECM) degradation may represent a mechanism for cardiac protection against ischemia. Extracellular matrix metalloproteinase inducer (EMMPRIN) is highly expressed in response to acute myocardial infarction (AMI), and induces activation of several matrix metalloprote...

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Autores principales: Cuadrado, Irene, Piedras, Maria Jose Garcia Miguel, Herruzo, Irene, Turpin, Maria del Carmen, Castejón, Borja, Reventun, Paula, Martin, Ana, Saura, Marta, Zamorano, Jose Luis, Zaragoza, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775864/
https://www.ncbi.nlm.nih.gov/pubmed/26941847
http://dx.doi.org/10.7150/thno.13352
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author Cuadrado, Irene
Piedras, Maria Jose Garcia Miguel
Herruzo, Irene
Turpin, Maria del Carmen
Castejón, Borja
Reventun, Paula
Martin, Ana
Saura, Marta
Zamorano, Jose Luis
Zaragoza, Carlos
author_facet Cuadrado, Irene
Piedras, Maria Jose Garcia Miguel
Herruzo, Irene
Turpin, Maria del Carmen
Castejón, Borja
Reventun, Paula
Martin, Ana
Saura, Marta
Zamorano, Jose Luis
Zaragoza, Carlos
author_sort Cuadrado, Irene
collection PubMed
description Inhibition of extracellular matrix (ECM) degradation may represent a mechanism for cardiac protection against ischemia. Extracellular matrix metalloproteinase inducer (EMMPRIN) is highly expressed in response to acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including gelatinases MMP-2 and MMP-9. We targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles conjugated with the EMMPRIN binding peptide AP-9 (NAP9), or an AP-9 scrambled peptide as a negative control (NAPSC). We found that NAP9 binds to endogenous EMMPRIN in cultured HL1 myocytes and in mouse hearts subjected to ischemia/reperfusion (IR). Injection of NAP9 at the time of or one day after IR, was enough to reduce progression of myocardial cell death when compared to Control and NAPSC injected mice (infarct size in NAP9 injected mice: 32%±6.59 vs Control: 46%±9.04 or NAPSC injected mice: 48%±7.64). In the same way, cardiac parameters were recovered to almost healthy levels (LVEF NAP9 63% ± 7.24 vs Control 42% ± 4.74 or NAPSC 39% ± 6.44), whereas ECM degradation was also reduced as shown by inhibition of MMP-2 and MMP-9 activation. Cardiac magnetic resonance (CMR) scans have shown a signal enhancement in the left ventricle of NAP9 injected mice with respect to non-injected, and to mice injected with NAPSC. A positive correlation between CMR enhancement and Evans-Blue/TTC staining of infarct size was calculated (R:0.65). Taken together, these results point to EMMPRIN targeted nanoparticles as a new approach to the mitigation of ischemic/reperfusion injury.
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spelling pubmed-47758642016-03-03 EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction Cuadrado, Irene Piedras, Maria Jose Garcia Miguel Herruzo, Irene Turpin, Maria del Carmen Castejón, Borja Reventun, Paula Martin, Ana Saura, Marta Zamorano, Jose Luis Zaragoza, Carlos Theranostics Research Paper Inhibition of extracellular matrix (ECM) degradation may represent a mechanism for cardiac protection against ischemia. Extracellular matrix metalloproteinase inducer (EMMPRIN) is highly expressed in response to acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including gelatinases MMP-2 and MMP-9. We targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles conjugated with the EMMPRIN binding peptide AP-9 (NAP9), or an AP-9 scrambled peptide as a negative control (NAPSC). We found that NAP9 binds to endogenous EMMPRIN in cultured HL1 myocytes and in mouse hearts subjected to ischemia/reperfusion (IR). Injection of NAP9 at the time of or one day after IR, was enough to reduce progression of myocardial cell death when compared to Control and NAPSC injected mice (infarct size in NAP9 injected mice: 32%±6.59 vs Control: 46%±9.04 or NAPSC injected mice: 48%±7.64). In the same way, cardiac parameters were recovered to almost healthy levels (LVEF NAP9 63% ± 7.24 vs Control 42% ± 4.74 or NAPSC 39% ± 6.44), whereas ECM degradation was also reduced as shown by inhibition of MMP-2 and MMP-9 activation. Cardiac magnetic resonance (CMR) scans have shown a signal enhancement in the left ventricle of NAP9 injected mice with respect to non-injected, and to mice injected with NAPSC. A positive correlation between CMR enhancement and Evans-Blue/TTC staining of infarct size was calculated (R:0.65). Taken together, these results point to EMMPRIN targeted nanoparticles as a new approach to the mitigation of ischemic/reperfusion injury. Ivyspring International Publisher 2016-02-15 /pmc/articles/PMC4775864/ /pubmed/26941847 http://dx.doi.org/10.7150/thno.13352 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Cuadrado, Irene
Piedras, Maria Jose Garcia Miguel
Herruzo, Irene
Turpin, Maria del Carmen
Castejón, Borja
Reventun, Paula
Martin, Ana
Saura, Marta
Zamorano, Jose Luis
Zaragoza, Carlos
EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction
title EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction
title_full EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction
title_fullStr EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction
title_full_unstemmed EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction
title_short EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction
title_sort emmprin-targeted magnetic nanoparticles for in vivo visualization and regression of acute myocardial infarction
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775864/
https://www.ncbi.nlm.nih.gov/pubmed/26941847
http://dx.doi.org/10.7150/thno.13352
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