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Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome

BACKGROUND: Ischemic heart disease continues to be a leading cause of mortality in patients. Extracellular vesicles (EVs) provide a potential for treatment that may induce collateral vessel growth to increase myocardial perfusion. METHODS AND RESULTS: Nineteen male Yorkshire pigs were given a high‐f...

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Autores principales: Scrimgeour, Laura A., Potz, Brittany A., Aboul Gheit, Ahmad, Shi, Guangbin, Stanley, Melissa, Zhang, Zhiqi, Sodha, Neel R., Ahsan, Nagib, Abid, M. Ruhul, Sellke, Frank W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761642/
https://www.ncbi.nlm.nih.gov/pubmed/31354010
http://dx.doi.org/10.1161/JAHA.119.012617
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author Scrimgeour, Laura A.
Potz, Brittany A.
Aboul Gheit, Ahmad
Shi, Guangbin
Stanley, Melissa
Zhang, Zhiqi
Sodha, Neel R.
Ahsan, Nagib
Abid, M. Ruhul
Sellke, Frank W.
author_facet Scrimgeour, Laura A.
Potz, Brittany A.
Aboul Gheit, Ahmad
Shi, Guangbin
Stanley, Melissa
Zhang, Zhiqi
Sodha, Neel R.
Ahsan, Nagib
Abid, M. Ruhul
Sellke, Frank W.
author_sort Scrimgeour, Laura A.
collection PubMed
description BACKGROUND: Ischemic heart disease continues to be a leading cause of mortality in patients. Extracellular vesicles (EVs) provide a potential for treatment that may induce collateral vessel growth to increase myocardial perfusion. METHODS AND RESULTS: Nineteen male Yorkshire pigs were given a high‐fat diet for 4 weeks, then underwent placement of an ameroid constrictor on the left circumflex artery to induce chronic myocardial ischemia. Two weeks later, the pigs received either intramyocardial vehicle (n=6), EVs (high‐fat diet with myocardial EV injection [HVM]; n=8), or HVM and calpain inhibition (n=5). Five weeks later, myocardial function, perfusion, coronary vascular density, and cell signaling were examined. Perfusion in the collateral‐dependent myocardium was increased during rapid ventricular pacing in the HVM group in both nonischemic (P=0.04) and ischemic areas of the ventricle (P=0.05). Cardiac output and stroke volume were significantly improved in the HVM group compared with the control group during ventricular pacing (P=0.006). Increased arteriolar density was seen in the HVM group in both nonischemic and ischemic myocardium (P=0.003 for both). However, no significant changes in the capillary density were observed between the control, HVM, and HVM and calpain inhibition groups (P=0.07). The group that received EVs with oral calpain inhibition had neither increased vessel density (P>0.99) nor improvement in blood flow or cardiac function (P=0.48) when compared with the control group. CONCLUSIONS: These findings suggest that EVs promote angiogenesis in areas of chronic myocardial ischemia and improve cardiac function under conditions of diet‐induced metabolic syndrome.
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spelling pubmed-67616422019-09-30 Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome Scrimgeour, Laura A. Potz, Brittany A. Aboul Gheit, Ahmad Shi, Guangbin Stanley, Melissa Zhang, Zhiqi Sodha, Neel R. Ahsan, Nagib Abid, M. Ruhul Sellke, Frank W. J Am Heart Assoc Original Research BACKGROUND: Ischemic heart disease continues to be a leading cause of mortality in patients. Extracellular vesicles (EVs) provide a potential for treatment that may induce collateral vessel growth to increase myocardial perfusion. METHODS AND RESULTS: Nineteen male Yorkshire pigs were given a high‐fat diet for 4 weeks, then underwent placement of an ameroid constrictor on the left circumflex artery to induce chronic myocardial ischemia. Two weeks later, the pigs received either intramyocardial vehicle (n=6), EVs (high‐fat diet with myocardial EV injection [HVM]; n=8), or HVM and calpain inhibition (n=5). Five weeks later, myocardial function, perfusion, coronary vascular density, and cell signaling were examined. Perfusion in the collateral‐dependent myocardium was increased during rapid ventricular pacing in the HVM group in both nonischemic (P=0.04) and ischemic areas of the ventricle (P=0.05). Cardiac output and stroke volume were significantly improved in the HVM group compared with the control group during ventricular pacing (P=0.006). Increased arteriolar density was seen in the HVM group in both nonischemic and ischemic myocardium (P=0.003 for both). However, no significant changes in the capillary density were observed between the control, HVM, and HVM and calpain inhibition groups (P=0.07). The group that received EVs with oral calpain inhibition had neither increased vessel density (P>0.99) nor improvement in blood flow or cardiac function (P=0.48) when compared with the control group. CONCLUSIONS: These findings suggest that EVs promote angiogenesis in areas of chronic myocardial ischemia and improve cardiac function under conditions of diet‐induced metabolic syndrome. John Wiley and Sons Inc. 2019-07-27 /pmc/articles/PMC6761642/ /pubmed/31354010 http://dx.doi.org/10.1161/JAHA.119.012617 Text en © 2019 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-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Scrimgeour, Laura A.
Potz, Brittany A.
Aboul Gheit, Ahmad
Shi, Guangbin
Stanley, Melissa
Zhang, Zhiqi
Sodha, Neel R.
Ahsan, Nagib
Abid, M. Ruhul
Sellke, Frank W.
Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome
title Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome
title_full Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome
title_fullStr Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome
title_full_unstemmed Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome
title_short Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome
title_sort extracellular vesicles promote arteriogenesis in chronically ischemic myocardium in the setting of metabolic syndrome
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761642/
https://www.ncbi.nlm.nih.gov/pubmed/31354010
http://dx.doi.org/10.1161/JAHA.119.012617
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