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Comparative Analysis of Normoxia- and Hypoxia-Modified Extracellular Vesicle Therapy in Function, Perfusion, and Collateralization in Chronically Ischemic Myocardium

We have previously shown that normoxia serum-starved extracellular vesicle (EV) therapy improves myocardial function, perfusion, and angiogenesis in a swine model of chronic myocardial ischemia. Hypoxia-modified EVs have increased abundance of anti-oxidant, pro-angiogenic, and pro-survival proteins....

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Autores principales: Sabe, Sharif A., Xu, Cynthia M., Potz, Brittany A., Malhotra, Akshay, Sabra, Mohamed, Harris, Dwight D., Broadwin, Mark, Abid, M. Ruhul, Sellke, Frank W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916784/
https://www.ncbi.nlm.nih.gov/pubmed/36768399
http://dx.doi.org/10.3390/ijms24032076
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author Sabe, Sharif A.
Xu, Cynthia M.
Potz, Brittany A.
Malhotra, Akshay
Sabra, Mohamed
Harris, Dwight D.
Broadwin, Mark
Abid, M. Ruhul
Sellke, Frank W.
author_facet Sabe, Sharif A.
Xu, Cynthia M.
Potz, Brittany A.
Malhotra, Akshay
Sabra, Mohamed
Harris, Dwight D.
Broadwin, Mark
Abid, M. Ruhul
Sellke, Frank W.
author_sort Sabe, Sharif A.
collection PubMed
description We have previously shown that normoxia serum-starved extracellular vesicle (EV) therapy improves myocardial function, perfusion, and angiogenesis in a swine model of chronic myocardial ischemia. Hypoxia-modified EVs have increased abundance of anti-oxidant, pro-angiogenic, and pro-survival proteins. The purpose of this study is to investigate the differential effects of normoxia serum-starved EVs and hypoxia-modified EVs on myocardial function, perfusion, and microvascular density in chronically ischemic myocardium. Yorkshire swine underwent placement of an ameroid constrictor to the left circumflex artery to induce chronic myocardial ischemia. Two weeks later, the pigs underwent intramyocardial injection of either normoxia serum-starved EVs (NOR, n = 10) or hypoxia-modified EVs (HYP, n = 7). Five weeks later, pigs were euthanized, and ischemic myocardium was harvested. Hypoxia EV treatment was associated with improved contractility compared to NOR, as well as improved capillary density, without changes in arteriolar density. There were trends towards improved perfusion at rest and during pacing in the HYP group compared to NOR. Ischemic myocardium in the HYP group had increased pro-angiogenic Akt and ERK signaling and decreased expression of anti-angiogenic markers compared to the NOR group. In the setting of chronic myocardial ischemia, hypoxia-modified EVs may enhance contractility, capillary density, and angiogenic signaling pathways compared to normoxia serum-starved EVs.
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spelling pubmed-99167842023-02-11 Comparative Analysis of Normoxia- and Hypoxia-Modified Extracellular Vesicle Therapy in Function, Perfusion, and Collateralization in Chronically Ischemic Myocardium Sabe, Sharif A. Xu, Cynthia M. Potz, Brittany A. Malhotra, Akshay Sabra, Mohamed Harris, Dwight D. Broadwin, Mark Abid, M. Ruhul Sellke, Frank W. Int J Mol Sci Article We have previously shown that normoxia serum-starved extracellular vesicle (EV) therapy improves myocardial function, perfusion, and angiogenesis in a swine model of chronic myocardial ischemia. Hypoxia-modified EVs have increased abundance of anti-oxidant, pro-angiogenic, and pro-survival proteins. The purpose of this study is to investigate the differential effects of normoxia serum-starved EVs and hypoxia-modified EVs on myocardial function, perfusion, and microvascular density in chronically ischemic myocardium. Yorkshire swine underwent placement of an ameroid constrictor to the left circumflex artery to induce chronic myocardial ischemia. Two weeks later, the pigs underwent intramyocardial injection of either normoxia serum-starved EVs (NOR, n = 10) or hypoxia-modified EVs (HYP, n = 7). Five weeks later, pigs were euthanized, and ischemic myocardium was harvested. Hypoxia EV treatment was associated with improved contractility compared to NOR, as well as improved capillary density, without changes in arteriolar density. There were trends towards improved perfusion at rest and during pacing in the HYP group compared to NOR. Ischemic myocardium in the HYP group had increased pro-angiogenic Akt and ERK signaling and decreased expression of anti-angiogenic markers compared to the NOR group. In the setting of chronic myocardial ischemia, hypoxia-modified EVs may enhance contractility, capillary density, and angiogenic signaling pathways compared to normoxia serum-starved EVs. MDPI 2023-01-20 /pmc/articles/PMC9916784/ /pubmed/36768399 http://dx.doi.org/10.3390/ijms24032076 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sabe, Sharif A.
Xu, Cynthia M.
Potz, Brittany A.
Malhotra, Akshay
Sabra, Mohamed
Harris, Dwight D.
Broadwin, Mark
Abid, M. Ruhul
Sellke, Frank W.
Comparative Analysis of Normoxia- and Hypoxia-Modified Extracellular Vesicle Therapy in Function, Perfusion, and Collateralization in Chronically Ischemic Myocardium
title Comparative Analysis of Normoxia- and Hypoxia-Modified Extracellular Vesicle Therapy in Function, Perfusion, and Collateralization in Chronically Ischemic Myocardium
title_full Comparative Analysis of Normoxia- and Hypoxia-Modified Extracellular Vesicle Therapy in Function, Perfusion, and Collateralization in Chronically Ischemic Myocardium
title_fullStr Comparative Analysis of Normoxia- and Hypoxia-Modified Extracellular Vesicle Therapy in Function, Perfusion, and Collateralization in Chronically Ischemic Myocardium
title_full_unstemmed Comparative Analysis of Normoxia- and Hypoxia-Modified Extracellular Vesicle Therapy in Function, Perfusion, and Collateralization in Chronically Ischemic Myocardium
title_short Comparative Analysis of Normoxia- and Hypoxia-Modified Extracellular Vesicle Therapy in Function, Perfusion, and Collateralization in Chronically Ischemic Myocardium
title_sort comparative analysis of normoxia- and hypoxia-modified extracellular vesicle therapy in function, perfusion, and collateralization in chronically ischemic myocardium
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9916784/
https://www.ncbi.nlm.nih.gov/pubmed/36768399
http://dx.doi.org/10.3390/ijms24032076
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