Deterioration of Cardiac Function After Acute Myocardial Infarction is Prevented by Transplantation of Modified Endothelial Progenitor Cells Overexpressing Endothelial NO Synthases

Background/Aims: Stem cell transplantation and gene therapies have been shown to attenuate myocardial dysfunction after myocardial infarction (AMI) in different acute and chronic animal models. The aim of this study was to assess the potential therapeutic efficacy of endothelial NO synthases (eNOS)-...

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Main Authors: Xiang Chen, Mingbiao Gu, Xianxian Zhao, Xing Zheng, Yongwen Qin, Xiaohua You
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2013-03-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/343373
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author Xiang Chen
Mingbiao Gu
Xianxian Zhao
Xing Zheng
Yongwen Qin
Xiaohua You
author_facet Xiang Chen
Mingbiao Gu
Xianxian Zhao
Xing Zheng
Yongwen Qin
Xiaohua You
author_sort Xiang Chen
collection DOAJ
description Background/Aims: Stem cell transplantation and gene therapies have been shown to attenuate myocardial dysfunction after myocardial infarction (AMI) in different acute and chronic animal models. The aim of this study was to assess the potential therapeutic efficacy of endothelial NO synthases (eNOS)-expressing endothelial progenitor cells (EPCs) on infarcted hearts. Methods: Lentiviral eNOS-infected EPCs were injected after 1 h of ligation of the left anterior descending artery (LAD). The pro-inflammatory cytokines TNF-α and IL-1β levels in cardiac tissue were measured by ELISA at 3 days after transplantation. 28 days post AMI (before sacrifice), Left ventricular function of each group was determined by echocardiography and pressure-volume system. Cardiac tissues were analyzed with hematoxylin and eosin (H&E) staining and immunohistochemisty. eNOS expression in cardiac tissues was detected by western blot, and NO production of cardiac tissues was determined using an NO assay kit. Results: TNF-α and IL-1β levels in cardiac tissue were decreased significantly at 3 days after transplantation of lentiviral with eNOS infected EPCs compared to medium control, eNOS lentiviral vector and normal EPCs. At the 28 day after AMI, echocardiography and hemodynamic measurements, and isolated heart studies showed great therapeutic efficacy in improvement of cardiac function, reduction of infarcted size and improvement of vascular densities in the peri-infarct region after intramyocardial application of lentiviral eNOS-infected EPCs compared to medium control, eNOS lentiviral vector and normal EPCs. The eNOS over-expression in cardiac tissue was observed in the eNOS-EPCs and eNOS lentiviral vector group, and NO levels were increased significantly in the eNOS-EPCs and eNOS lentiviral vector group compared to the other three groups (sham operated group, transplantation of medium or EPCs group). Conclusion: EPCs can be an attractive vehicle for the exogenous eNOS expression into heart after infarction, which is beneficial to prevent deterioration and promote restoration of cardiac function after AMI by improving angiogenesis.
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spelling doaj.art-a6c167547b824097936394527d73f0e72022-12-22T01:54:41ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782013-03-01312-335536510.1159/000343373343373Deterioration of Cardiac Function After Acute Myocardial Infarction is Prevented by Transplantation of Modified Endothelial Progenitor Cells Overexpressing Endothelial NO SynthasesXiang ChenMingbiao GuXianxian ZhaoXing ZhengYongwen QinXiaohua YouBackground/Aims: Stem cell transplantation and gene therapies have been shown to attenuate myocardial dysfunction after myocardial infarction (AMI) in different acute and chronic animal models. The aim of this study was to assess the potential therapeutic efficacy of endothelial NO synthases (eNOS)-expressing endothelial progenitor cells (EPCs) on infarcted hearts. Methods: Lentiviral eNOS-infected EPCs were injected after 1 h of ligation of the left anterior descending artery (LAD). The pro-inflammatory cytokines TNF-α and IL-1β levels in cardiac tissue were measured by ELISA at 3 days after transplantation. 28 days post AMI (before sacrifice), Left ventricular function of each group was determined by echocardiography and pressure-volume system. Cardiac tissues were analyzed with hematoxylin and eosin (H&E) staining and immunohistochemisty. eNOS expression in cardiac tissues was detected by western blot, and NO production of cardiac tissues was determined using an NO assay kit. Results: TNF-α and IL-1β levels in cardiac tissue were decreased significantly at 3 days after transplantation of lentiviral with eNOS infected EPCs compared to medium control, eNOS lentiviral vector and normal EPCs. At the 28 day after AMI, echocardiography and hemodynamic measurements, and isolated heart studies showed great therapeutic efficacy in improvement of cardiac function, reduction of infarcted size and improvement of vascular densities in the peri-infarct region after intramyocardial application of lentiviral eNOS-infected EPCs compared to medium control, eNOS lentiviral vector and normal EPCs. The eNOS over-expression in cardiac tissue was observed in the eNOS-EPCs and eNOS lentiviral vector group, and NO levels were increased significantly in the eNOS-EPCs and eNOS lentiviral vector group compared to the other three groups (sham operated group, transplantation of medium or EPCs group). Conclusion: EPCs can be an attractive vehicle for the exogenous eNOS expression into heart after infarction, which is beneficial to prevent deterioration and promote restoration of cardiac function after AMI by improving angiogenesis.http://www.karger.com/Article/FullText/343373Endothelial progenitor cellsEndothelial NO synthasesAcute myocardial infarctionCell transplantation
spellingShingle Xiang Chen
Mingbiao Gu
Xianxian Zhao
Xing Zheng
Yongwen Qin
Xiaohua You
Deterioration of Cardiac Function After Acute Myocardial Infarction is Prevented by Transplantation of Modified Endothelial Progenitor Cells Overexpressing Endothelial NO Synthases
Cellular Physiology and Biochemistry
Endothelial progenitor cells
Endothelial NO synthases
Acute myocardial infarction
Cell transplantation
title Deterioration of Cardiac Function After Acute Myocardial Infarction is Prevented by Transplantation of Modified Endothelial Progenitor Cells Overexpressing Endothelial NO Synthases
title_full Deterioration of Cardiac Function After Acute Myocardial Infarction is Prevented by Transplantation of Modified Endothelial Progenitor Cells Overexpressing Endothelial NO Synthases
title_fullStr Deterioration of Cardiac Function After Acute Myocardial Infarction is Prevented by Transplantation of Modified Endothelial Progenitor Cells Overexpressing Endothelial NO Synthases
title_full_unstemmed Deterioration of Cardiac Function After Acute Myocardial Infarction is Prevented by Transplantation of Modified Endothelial Progenitor Cells Overexpressing Endothelial NO Synthases
title_short Deterioration of Cardiac Function After Acute Myocardial Infarction is Prevented by Transplantation of Modified Endothelial Progenitor Cells Overexpressing Endothelial NO Synthases
title_sort deterioration of cardiac function after acute myocardial infarction is prevented by transplantation of modified endothelial progenitor cells overexpressing endothelial no synthases
topic Endothelial progenitor cells
Endothelial NO synthases
Acute myocardial infarction
Cell transplantation
url http://www.karger.com/Article/FullText/343373
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