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Preconditioning via Angiotensin Type 2 Receptor Activation Improves Therapeutic Efficacy of Bone Marrow Mononuclear Cells for Cardiac Repair
BACKGROUND: The therapeutic efficiency of bone marrow mononuclear cells (BMMNCs) autologous transplantation for myocardial infarction (MI) remains low. Here we developed a novel strategy to improve cardiac repair by preconditioning BMMNCs via angiotensin II type 2 receptor (AT2R) stimulation. METHOD...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858344/ https://www.ncbi.nlm.nih.gov/pubmed/24340072 http://dx.doi.org/10.1371/journal.pone.0082997 |
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author | Xu, Yinchuan Hu, Xinyang Wang, Lihan Jiang, Zhi Liu, Xianbao Yu, Hong Zhang, Zhaocai Chen, Huiqiang Chen, Han Steinhoff, Gustav Li, Jun Jian’an Wang, |
author_facet | Xu, Yinchuan Hu, Xinyang Wang, Lihan Jiang, Zhi Liu, Xianbao Yu, Hong Zhang, Zhaocai Chen, Huiqiang Chen, Han Steinhoff, Gustav Li, Jun Jian’an Wang, |
author_sort | Xu, Yinchuan |
collection | PubMed |
description | BACKGROUND: The therapeutic efficiency of bone marrow mononuclear cells (BMMNCs) autologous transplantation for myocardial infarction (MI) remains low. Here we developed a novel strategy to improve cardiac repair by preconditioning BMMNCs via angiotensin II type 2 receptor (AT2R) stimulation. METHODS AND RESULTS: Acute MI in rats led to a significant increase of AT2R expression in BMMNCs. Preconditioning of BMMNCs via AT2R stimulation directly with an AT2R agonist CGP42112A or indirectly with angiotensin II plus AT1R antagonist valsartan led to ERK activation and increased eNOS expression as well as subsequent nitric oxide generation, ultimately improved cardiomyocyte protection in vitro as measured by co-culture approach. Intramyocardial transplantation of BMMNCs preconditioned via AT2R stimulation improved survival of transplanted cells in ischemic region of heart tissue and reduced cardiomyocyte apoptosis and inflammation at 3 days after MI. At 4 weeks after transplantation, compared to DMEM and non-preconditioned BMMNCs group, AT2R stimulated BMMNCs group showed enhanced vessel density in peri-infarct region and attenuated infarct size, leading to global heart function improvement. CONCLUSIONS: Preconditioning of BMMNCs via AT2R stimulation exerts protective effect against MI. Stimulation of AT2R in BMMNCs may provide a new strategy to improving therapeutic efficiency of stem cells for post MI cardiac repair. |
format | Online Article Text |
id | pubmed-3858344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38583442013-12-11 Preconditioning via Angiotensin Type 2 Receptor Activation Improves Therapeutic Efficacy of Bone Marrow Mononuclear Cells for Cardiac Repair Xu, Yinchuan Hu, Xinyang Wang, Lihan Jiang, Zhi Liu, Xianbao Yu, Hong Zhang, Zhaocai Chen, Huiqiang Chen, Han Steinhoff, Gustav Li, Jun Jian’an Wang, PLoS One Research Article BACKGROUND: The therapeutic efficiency of bone marrow mononuclear cells (BMMNCs) autologous transplantation for myocardial infarction (MI) remains low. Here we developed a novel strategy to improve cardiac repair by preconditioning BMMNCs via angiotensin II type 2 receptor (AT2R) stimulation. METHODS AND RESULTS: Acute MI in rats led to a significant increase of AT2R expression in BMMNCs. Preconditioning of BMMNCs via AT2R stimulation directly with an AT2R agonist CGP42112A or indirectly with angiotensin II plus AT1R antagonist valsartan led to ERK activation and increased eNOS expression as well as subsequent nitric oxide generation, ultimately improved cardiomyocyte protection in vitro as measured by co-culture approach. Intramyocardial transplantation of BMMNCs preconditioned via AT2R stimulation improved survival of transplanted cells in ischemic region of heart tissue and reduced cardiomyocyte apoptosis and inflammation at 3 days after MI. At 4 weeks after transplantation, compared to DMEM and non-preconditioned BMMNCs group, AT2R stimulated BMMNCs group showed enhanced vessel density in peri-infarct region and attenuated infarct size, leading to global heart function improvement. CONCLUSIONS: Preconditioning of BMMNCs via AT2R stimulation exerts protective effect against MI. Stimulation of AT2R in BMMNCs may provide a new strategy to improving therapeutic efficiency of stem cells for post MI cardiac repair. Public Library of Science 2013-12-10 /pmc/articles/PMC3858344/ /pubmed/24340072 http://dx.doi.org/10.1371/journal.pone.0082997 Text en © 2013 Xu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Xu, Yinchuan Hu, Xinyang Wang, Lihan Jiang, Zhi Liu, Xianbao Yu, Hong Zhang, Zhaocai Chen, Huiqiang Chen, Han Steinhoff, Gustav Li, Jun Jian’an Wang, Preconditioning via Angiotensin Type 2 Receptor Activation Improves Therapeutic Efficacy of Bone Marrow Mononuclear Cells for Cardiac Repair |
title | Preconditioning via Angiotensin Type 2 Receptor Activation Improves Therapeutic Efficacy of Bone Marrow Mononuclear Cells for Cardiac Repair |
title_full | Preconditioning via Angiotensin Type 2 Receptor Activation Improves Therapeutic Efficacy of Bone Marrow Mononuclear Cells for Cardiac Repair |
title_fullStr | Preconditioning via Angiotensin Type 2 Receptor Activation Improves Therapeutic Efficacy of Bone Marrow Mononuclear Cells for Cardiac Repair |
title_full_unstemmed | Preconditioning via Angiotensin Type 2 Receptor Activation Improves Therapeutic Efficacy of Bone Marrow Mononuclear Cells for Cardiac Repair |
title_short | Preconditioning via Angiotensin Type 2 Receptor Activation Improves Therapeutic Efficacy of Bone Marrow Mononuclear Cells for Cardiac Repair |
title_sort | preconditioning via angiotensin type 2 receptor activation improves therapeutic efficacy of bone marrow mononuclear cells for cardiac repair |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858344/ https://www.ncbi.nlm.nih.gov/pubmed/24340072 http://dx.doi.org/10.1371/journal.pone.0082997 |
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