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Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis

Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate the consequences of MI are a high priority. Cardiac progenitor cells (CPCs) have been used to treat cardiac injury post-MI, and despite poor engraftment, they have been show...

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Autores principales: Youn, Seock-Won, Li, Yang, Kim, Young-Mee, Sudhahar, Varadarajan, Abdelsaid, Kareem, Kim, Ha Won, Liu, Yutao, Fulton, David J.R., Ashraf, Muhammad, Tang, Yaoliang, Fukai, Tohru, Ushio-Fukai, Masuko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356993/
https://www.ncbi.nlm.nih.gov/pubmed/30634641
http://dx.doi.org/10.3390/antiox8010018
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author Youn, Seock-Won
Li, Yang
Kim, Young-Mee
Sudhahar, Varadarajan
Abdelsaid, Kareem
Kim, Ha Won
Liu, Yutao
Fulton, David J.R.
Ashraf, Muhammad
Tang, Yaoliang
Fukai, Tohru
Ushio-Fukai, Masuko
author_facet Youn, Seock-Won
Li, Yang
Kim, Young-Mee
Sudhahar, Varadarajan
Abdelsaid, Kareem
Kim, Ha Won
Liu, Yutao
Fulton, David J.R.
Ashraf, Muhammad
Tang, Yaoliang
Fukai, Tohru
Ushio-Fukai, Masuko
author_sort Youn, Seock-Won
collection PubMed
description Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate the consequences of MI are a high priority. Cardiac progenitor cells (CPCs) have been used to treat cardiac injury post-MI, and despite poor engraftment, they have been shown to inhibit apoptosis and to promote angiogenesis through poorly understood paracrine effects. We previously reported that the direct injection of exosomes derived from CPCs (CPCexo) into mouse hearts provides protection against apoptosis in a model of acute ischemia/reperfusion injury. Moreover, we and others have reported that reactive oxygen species (ROS) derived from NADPH oxidase (NOX) can enhance angiogenesis in endothelial cells (ECs). Here we examined whether bioengineered CPCexo transfected with a pro-angiogenic miR-322 (CPCexo-322) can improve therapeutic efficacy in a mouse model of MI as compared to CPCexo. Systemic administration of CPCexo-322 in mice after ischemic injury provided greater protection post-MI than control CPCexo, in part, through enhanced angiogenesis in the border zones of infarcted hearts. Mechanistically, the treatment of cultured human ECs with CPCexo-322 resulted in a greater angiogenic response, as determined by increased EC migration and capillary tube formation via increased Nox2-derived ROS. Our study reveals that the engineering of CPCexo via microRNA (miR) programing can enhance angiogenesis, and this may be an effective therapeutic strategy for the treatment of ischemic cardiovascular diseases.
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spelling pubmed-63569932019-02-04 Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis Youn, Seock-Won Li, Yang Kim, Young-Mee Sudhahar, Varadarajan Abdelsaid, Kareem Kim, Ha Won Liu, Yutao Fulton, David J.R. Ashraf, Muhammad Tang, Yaoliang Fukai, Tohru Ushio-Fukai, Masuko Antioxidants (Basel) Article Myocardial infarction (MI) is the primary cause of cardiovascular mortality, and therapeutic strategies to prevent or mitigate the consequences of MI are a high priority. Cardiac progenitor cells (CPCs) have been used to treat cardiac injury post-MI, and despite poor engraftment, they have been shown to inhibit apoptosis and to promote angiogenesis through poorly understood paracrine effects. We previously reported that the direct injection of exosomes derived from CPCs (CPCexo) into mouse hearts provides protection against apoptosis in a model of acute ischemia/reperfusion injury. Moreover, we and others have reported that reactive oxygen species (ROS) derived from NADPH oxidase (NOX) can enhance angiogenesis in endothelial cells (ECs). Here we examined whether bioengineered CPCexo transfected with a pro-angiogenic miR-322 (CPCexo-322) can improve therapeutic efficacy in a mouse model of MI as compared to CPCexo. Systemic administration of CPCexo-322 in mice after ischemic injury provided greater protection post-MI than control CPCexo, in part, through enhanced angiogenesis in the border zones of infarcted hearts. Mechanistically, the treatment of cultured human ECs with CPCexo-322 resulted in a greater angiogenic response, as determined by increased EC migration and capillary tube formation via increased Nox2-derived ROS. Our study reveals that the engineering of CPCexo via microRNA (miR) programing can enhance angiogenesis, and this may be an effective therapeutic strategy for the treatment of ischemic cardiovascular diseases. MDPI 2019-01-10 /pmc/articles/PMC6356993/ /pubmed/30634641 http://dx.doi.org/10.3390/antiox8010018 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Youn, Seock-Won
Li, Yang
Kim, Young-Mee
Sudhahar, Varadarajan
Abdelsaid, Kareem
Kim, Ha Won
Liu, Yutao
Fulton, David J.R.
Ashraf, Muhammad
Tang, Yaoliang
Fukai, Tohru
Ushio-Fukai, Masuko
Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis
title Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis
title_full Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis
title_fullStr Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis
title_full_unstemmed Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis
title_short Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis
title_sort modification of cardiac progenitor cell-derived exosomes by mir-322 provides protection against myocardial infarction through nox2-dependent angiogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356993/
https://www.ncbi.nlm.nih.gov/pubmed/30634641
http://dx.doi.org/10.3390/antiox8010018
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