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Dynamics of angiogenesis in ischemic areas of the infarcted heart
Cardiomyocytes are susceptible to apoptosis caused by hypoxia during the acute and subacute phases of myocardial infarction (MI). Angiogenesis can reduce MI-induced damage by mitigating hypoxia. It has been speculated that the ischemic border zone is a unique area rescued by angiogenic therapy. Howe...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540926/ https://www.ncbi.nlm.nih.gov/pubmed/28769049 http://dx.doi.org/10.1038/s41598-017-07524-x |
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author | Kobayashi, Koichi Maeda, Kengo Takefuji, Mikito Kikuchi, Ryosuke Morishita, Yoshihiro Hirashima, Masanori Murohara, Toyoaki |
author_facet | Kobayashi, Koichi Maeda, Kengo Takefuji, Mikito Kikuchi, Ryosuke Morishita, Yoshihiro Hirashima, Masanori Murohara, Toyoaki |
author_sort | Kobayashi, Koichi |
collection | PubMed |
description | Cardiomyocytes are susceptible to apoptosis caused by hypoxia during the acute and subacute phases of myocardial infarction (MI). Angiogenesis can reduce MI-induced damage by mitigating hypoxia. It has been speculated that the ischemic border zone is a unique area rescued by angiogenic therapy. However, the mechanism and timing for new vessel formation in the mammalian heart following hypoxia are unclear. Identifying targets that benefit from angiogenesis treatment is indispensable for the development of revolutionary therapies. Here, we describe a novel circulatory system wherein new vessels develop from the endocardium of the left ventricle to perfuse the hypoxic area and salvage damaged cardiomyocytes at 3–14 days after MI by activating vascular endothelial growth factor signaling. Moreover, enhanced angiogenesis increased cardiomyocyte survival along the endocardium in the ischemic zone and suppressed ventricular remodeling in infarcted hearts. In contrast, cardiomyocytes in the border zone’s hypoxic area underwent apoptosis within 12 h of MI, and the border area that was amenable to treatment disappeared. These data indicate that the non-perfused area along the endocardium is a site of active angiogenesis and a promising target for MI treatment. |
format | Online Article Text |
id | pubmed-5540926 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55409262017-08-07 Dynamics of angiogenesis in ischemic areas of the infarcted heart Kobayashi, Koichi Maeda, Kengo Takefuji, Mikito Kikuchi, Ryosuke Morishita, Yoshihiro Hirashima, Masanori Murohara, Toyoaki Sci Rep Article Cardiomyocytes are susceptible to apoptosis caused by hypoxia during the acute and subacute phases of myocardial infarction (MI). Angiogenesis can reduce MI-induced damage by mitigating hypoxia. It has been speculated that the ischemic border zone is a unique area rescued by angiogenic therapy. However, the mechanism and timing for new vessel formation in the mammalian heart following hypoxia are unclear. Identifying targets that benefit from angiogenesis treatment is indispensable for the development of revolutionary therapies. Here, we describe a novel circulatory system wherein new vessels develop from the endocardium of the left ventricle to perfuse the hypoxic area and salvage damaged cardiomyocytes at 3–14 days after MI by activating vascular endothelial growth factor signaling. Moreover, enhanced angiogenesis increased cardiomyocyte survival along the endocardium in the ischemic zone and suppressed ventricular remodeling in infarcted hearts. In contrast, cardiomyocytes in the border zone’s hypoxic area underwent apoptosis within 12 h of MI, and the border area that was amenable to treatment disappeared. These data indicate that the non-perfused area along the endocardium is a site of active angiogenesis and a promising target for MI treatment. Nature Publishing Group UK 2017-08-02 /pmc/articles/PMC5540926/ /pubmed/28769049 http://dx.doi.org/10.1038/s41598-017-07524-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kobayashi, Koichi Maeda, Kengo Takefuji, Mikito Kikuchi, Ryosuke Morishita, Yoshihiro Hirashima, Masanori Murohara, Toyoaki Dynamics of angiogenesis in ischemic areas of the infarcted heart |
title | Dynamics of angiogenesis in ischemic areas of the infarcted heart |
title_full | Dynamics of angiogenesis in ischemic areas of the infarcted heart |
title_fullStr | Dynamics of angiogenesis in ischemic areas of the infarcted heart |
title_full_unstemmed | Dynamics of angiogenesis in ischemic areas of the infarcted heart |
title_short | Dynamics of angiogenesis in ischemic areas of the infarcted heart |
title_sort | dynamics of angiogenesis in ischemic areas of the infarcted heart |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540926/ https://www.ncbi.nlm.nih.gov/pubmed/28769049 http://dx.doi.org/10.1038/s41598-017-07524-x |
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