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Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia

BACKGROUND: Mesenchymal stem cell–derived extracellular vesicles (EVs) are believed to be cardioprotective in myocardial infarct. The objective of this study was to examine the effects of human mesenchymal cell–derived EV injection on cardiac function, myocardial blood flow, and vessel density in th...

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Autores principales: Potz, Brittany A., Scrimgeour, Laura A., Pavlov, Vasile I., Sodha, Neel R., Abid, M. Ruhul, Sellke, Frank W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220556/
https://www.ncbi.nlm.nih.gov/pubmed/29895586
http://dx.doi.org/10.1161/JAHA.117.008344
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author Potz, Brittany A.
Scrimgeour, Laura A.
Pavlov, Vasile I.
Sodha, Neel R.
Abid, M. Ruhul
Sellke, Frank W.
author_facet Potz, Brittany A.
Scrimgeour, Laura A.
Pavlov, Vasile I.
Sodha, Neel R.
Abid, M. Ruhul
Sellke, Frank W.
author_sort Potz, Brittany A.
collection PubMed
description BACKGROUND: Mesenchymal stem cell–derived extracellular vesicles (EVs) are believed to be cardioprotective in myocardial infarct. The objective of this study was to examine the effects of human mesenchymal cell–derived EV injection on cardiac function, myocardial blood flow, and vessel density in the setting of chronic myocardial ischemia. METHODS AND RESULTS: Twenty‐three Yorkshire swine underwent placement of an ameroid constrictor on their left circumflex artery. Two weeks later, the animals were split into 2 groups: the control group (CON; n=7) and the EV myocardial injection group (MVM; n=10). The MVM group underwent myocardial injection of 50 μg of EVs in 2 mL 0.9% saline into the ischemic myocardium. Five weeks later, the pigs underwent a harvest procedure, and the left ventricular myocardium was analyzed. Absolute blood flow and the ischemic/nonischemic myocardial perfusion ratio were increased in the ischemic myocardium in the MVM group compared with the CON group. Pigs in the MVM group had increased capillary and arteriolar density in the ischemic myocardial tissue compared with CON pigs. There was an increase in expression of the phospho–mitogen‐activated protein kinase/mitogen‐activated protein kinase ratio, the phospho–endothelial nitric oxide synthase/endothelial nitric oxide synthase ratio, and total protein kinase B in the MVM group compared with CON. There was an increase in cardiac output and stroke volume in the MVM group compared with CON. CONCLUSIONS: In the setting of chronic myocardial ischemia, myocardial injection of human mesenchymal cell–derived EVs increases blood flow to ischemic myocardial tissue by induction of capillary and arteriolar growth via activation of the protein kinase B/endothelial nitric oxide synthase and mitogen‐activated protein kinase signaling pathways resulting in increased cardiac output and stroke volume.
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spelling pubmed-62205562018-11-15 Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia Potz, Brittany A. Scrimgeour, Laura A. Pavlov, Vasile I. Sodha, Neel R. Abid, M. Ruhul Sellke, Frank W. J Am Heart Assoc Original Research BACKGROUND: Mesenchymal stem cell–derived extracellular vesicles (EVs) are believed to be cardioprotective in myocardial infarct. The objective of this study was to examine the effects of human mesenchymal cell–derived EV injection on cardiac function, myocardial blood flow, and vessel density in the setting of chronic myocardial ischemia. METHODS AND RESULTS: Twenty‐three Yorkshire swine underwent placement of an ameroid constrictor on their left circumflex artery. Two weeks later, the animals were split into 2 groups: the control group (CON; n=7) and the EV myocardial injection group (MVM; n=10). The MVM group underwent myocardial injection of 50 μg of EVs in 2 mL 0.9% saline into the ischemic myocardium. Five weeks later, the pigs underwent a harvest procedure, and the left ventricular myocardium was analyzed. Absolute blood flow and the ischemic/nonischemic myocardial perfusion ratio were increased in the ischemic myocardium in the MVM group compared with the CON group. Pigs in the MVM group had increased capillary and arteriolar density in the ischemic myocardial tissue compared with CON pigs. There was an increase in expression of the phospho–mitogen‐activated protein kinase/mitogen‐activated protein kinase ratio, the phospho–endothelial nitric oxide synthase/endothelial nitric oxide synthase ratio, and total protein kinase B in the MVM group compared with CON. There was an increase in cardiac output and stroke volume in the MVM group compared with CON. CONCLUSIONS: In the setting of chronic myocardial ischemia, myocardial injection of human mesenchymal cell–derived EVs increases blood flow to ischemic myocardial tissue by induction of capillary and arteriolar growth via activation of the protein kinase B/endothelial nitric oxide synthase and mitogen‐activated protein kinase signaling pathways resulting in increased cardiac output and stroke volume. John Wiley and Sons Inc. 2018-06-12 /pmc/articles/PMC6220556/ /pubmed/29895586 http://dx.doi.org/10.1161/JAHA.117.008344 Text en © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Research
Potz, Brittany A.
Scrimgeour, Laura A.
Pavlov, Vasile I.
Sodha, Neel R.
Abid, M. Ruhul
Sellke, Frank W.
Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia
title Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia
title_full Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia
title_fullStr Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia
title_full_unstemmed Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia
title_short Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia
title_sort extracellular vesicle injection improves myocardial function and increases angiogenesis in a swine model of chronic ischemia
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220556/
https://www.ncbi.nlm.nih.gov/pubmed/29895586
http://dx.doi.org/10.1161/JAHA.117.008344
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