Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling
Small and large preclinical animal models have shown that antagomir-92a-based therapy reduces early postischemic loss of function, but its effect on postinfarction remodeling is not known. In addition, the reported remote miR-92a inhibition in noncardiac organs prevents the translation of nonvectori...
| Autores: | , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:185098 |
| Acceso en línea: | https://ddd.uab.cat/record/185098 https://dx.doi.org/urn:doi:10.1161/JAHA.114.000946 |
| Access Level: | acceso abierto |
| Palabra clave: | Angiogenesis Antagomir Heart failure MicroRNA Myocardial infarction Remodeling |
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Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct RemodelingBellera Gotarda, Neus|||0000-0002-1040-0900Barba, Ignasi|||0000-0001-9886-3776Rodríguez Sinovas, Antonio|||0000-0003-2930-8773Ferret, EulaliaAsín, Miguel AngelGonzalez-Alujas, MªTeresaPérez-Rodón, Jordi|||0000-0003-2234-5248Esteves, MarielleFonseca, CarlaToran, NuriaGarcía del Blanco, Bruno|||0000-0002-4527-1600Pérez, AmadeoGarcía-Dorado, David|||0000-0002-1126-1279AngiogenesisAntagomirHeart failureMicroRNAMyocardial infarctionRemodelingSmall and large preclinical animal models have shown that antagomir-92a-based therapy reduces early postischemic loss of function, but its effect on postinfarction remodeling is not known. In addition, the reported remote miR-92a inhibition in noncardiac organs prevents the translation of nonvectorized miR-targeted therapy to the clinical setting. We investigated whether a single intracoronary administration of antagomir-92a encapsulated in microspheres could prevent deleterious remodeling of myocardium 1 month after acute myocardial infarction AUTHOR: Should "acute" be added before "myocardial infarction" (since abbreviation is AMI)? Also check at first mention in main text (AMI) without adverse effects. In a percutaneous pig model of reperfused AMI, a single intracoronary administration of antagomir-92a encapsulated in specific microspheres (9 μm poly-d,-lactide-co-glycolide [PLGA]) inhibited miR-92a in a local, selective, and sustained manner (n=3 pigs euthanized 1, 3, and 10 days after treatment; 8×, 2×, and 5×-fold inhibition at 1, 3, and 10 days). Downregulation of miR-92a resulted in significant vessel growth (n=27 adult minipigs randomly allocated to blind receive encapsulated antagomir-92a, encapsulated placebo, or saline [n=8, 9, 9]; P =0.001), reduced regional wall-motion dysfunction (P =0.03), and prevented adverse remodeling in the infarct area 1 month after injury (P =0.03). Intracoronary injection of microspheres had no significant adverse effect in downstream myocardium in healthy pigs (n=2), and fluorescein isothiocyanate albumin-PLGA microspheres were not found in myocardium outside the left anterior descending coronary artery territory (n=4) or in other organs (n=2). Early single intracoronary administration of encapsulated antagomir-92a in an adult pig model of reperfused AMI prevents left ventricular remodeling with no local or distant adverse effects, emerging as a promising therapeutic approach to translate to patients who suffer a large AMI.Universitat Autònoma de Barcelona 22014-01-0120142014-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/185098https://dx.doi.org/urn:doi:10.1161/JAHA.114.000946reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 SAF2008-03067Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD12-0042-0021open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1850982026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling |
| title |
Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling |
| spellingShingle |
Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling Bellera Gotarda, Neus|||0000-0002-1040-0900 Angiogenesis Antagomir Heart failure MicroRNA Myocardial infarction Remodeling |
| title_short |
Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling |
| title_full |
Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling |
| title_fullStr |
Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling |
| title_full_unstemmed |
Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling |
| title_sort |
Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling |
| dc.creator.none.fl_str_mv |
Bellera Gotarda, Neus|||0000-0002-1040-0900 Barba, Ignasi|||0000-0001-9886-3776 Rodríguez Sinovas, Antonio|||0000-0003-2930-8773 Ferret, Eulalia Asín, Miguel Angel Gonzalez-Alujas, MªTeresa Pérez-Rodón, Jordi|||0000-0003-2234-5248 Esteves, Marielle Fonseca, Carla Toran, Nuria García del Blanco, Bruno|||0000-0002-4527-1600 Pérez, Amadeo García-Dorado, David|||0000-0002-1126-1279 |
| author |
Bellera Gotarda, Neus|||0000-0002-1040-0900 |
| author_facet |
Bellera Gotarda, Neus|||0000-0002-1040-0900 Barba, Ignasi|||0000-0001-9886-3776 Rodríguez Sinovas, Antonio|||0000-0003-2930-8773 Ferret, Eulalia Asín, Miguel Angel Gonzalez-Alujas, MªTeresa Pérez-Rodón, Jordi|||0000-0003-2234-5248 Esteves, Marielle Fonseca, Carla Toran, Nuria García del Blanco, Bruno|||0000-0002-4527-1600 Pérez, Amadeo García-Dorado, David|||0000-0002-1126-1279 |
| author_role |
author |
| author2 |
Barba, Ignasi|||0000-0001-9886-3776 Rodríguez Sinovas, Antonio|||0000-0003-2930-8773 Ferret, Eulalia Asín, Miguel Angel Gonzalez-Alujas, MªTeresa Pérez-Rodón, Jordi|||0000-0003-2234-5248 Esteves, Marielle Fonseca, Carla Toran, Nuria García del Blanco, Bruno|||0000-0002-4527-1600 Pérez, Amadeo García-Dorado, David|||0000-0002-1126-1279 |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Angiogenesis Antagomir Heart failure MicroRNA Myocardial infarction Remodeling |
| topic |
Angiogenesis Antagomir Heart failure MicroRNA Myocardial infarction Remodeling |
| description |
Small and large preclinical animal models have shown that antagomir-92a-based therapy reduces early postischemic loss of function, but its effect on postinfarction remodeling is not known. In addition, the reported remote miR-92a inhibition in noncardiac organs prevents the translation of nonvectorized miR-targeted therapy to the clinical setting. We investigated whether a single intracoronary administration of antagomir-92a encapsulated in microspheres could prevent deleterious remodeling of myocardium 1 month after acute myocardial infarction AUTHOR: Should "acute" be added before "myocardial infarction" (since abbreviation is AMI)? Also check at first mention in main text (AMI) without adverse effects. In a percutaneous pig model of reperfused AMI, a single intracoronary administration of antagomir-92a encapsulated in specific microspheres (9 μm poly-d,-lactide-co-glycolide [PLGA]) inhibited miR-92a in a local, selective, and sustained manner (n=3 pigs euthanized 1, 3, and 10 days after treatment; 8×, 2×, and 5×-fold inhibition at 1, 3, and 10 days). Downregulation of miR-92a resulted in significant vessel growth (n=27 adult minipigs randomly allocated to blind receive encapsulated antagomir-92a, encapsulated placebo, or saline [n=8, 9, 9]; P =0.001), reduced regional wall-motion dysfunction (P =0.03), and prevented adverse remodeling in the infarct area 1 month after injury (P =0.03). Intracoronary injection of microspheres had no significant adverse effect in downstream myocardium in healthy pigs (n=2), and fluorescein isothiocyanate albumin-PLGA microspheres were not found in myocardium outside the left anterior descending coronary artery territory (n=4) or in other organs (n=2). Early single intracoronary administration of encapsulated antagomir-92a in an adult pig model of reperfused AMI prevents left ventricular remodeling with no local or distant adverse effects, emerging as a promising therapeutic approach to translate to patients who suffer a large AMI. |
| publishDate |
2014 |
| dc.date.none.fl_str_mv |
2 2014-01-01 2014 2014-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/185098 https://dx.doi.org/urn:doi:10.1161/JAHA.114.000946 |
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https://ddd.uab.cat/record/185098 https://dx.doi.org/urn:doi:10.1161/JAHA.114.000946 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 SAF2008-03067 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD12-0042-0021 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc/4.0/ |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by-nc/4.0/ |
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openAccess |
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