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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
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.
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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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