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FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs
The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4)...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963928/ https://www.ncbi.nlm.nih.gov/pubmed/24663349 http://dx.doi.org/10.1371/journal.pone.0092626 |
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author | Nakayoshi, Takaharu Sasaki, Ken-ichiro Kajimoto, Hidemi Koiwaya, Hiroshi Ohtsuka, Masanori Ueno, Takafumi Chibana, Hidetoshi Itaya, Naoki Sasaki, Masahiro Yokoyama, Shinji Fukumoto, Yoshihiro Imaizumi, Tsutomu |
author_facet | Nakayoshi, Takaharu Sasaki, Ken-ichiro Kajimoto, Hidemi Koiwaya, Hiroshi Ohtsuka, Masanori Ueno, Takafumi Chibana, Hidetoshi Itaya, Naoki Sasaki, Masahiro Yokoyama, Shinji Fukumoto, Yoshihiro Imaizumi, Tsutomu |
author_sort | Nakayoshi, Takaharu |
collection | PubMed |
description | The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play a pivotal role in apoptosis signaling of EPCs in response to oxidative stress. Accordingly, we assessed whether FOXO4-knockdown EPCs (FOXO4(KD)-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs. We transfected small interfering RNA targeted against FOXO4 of human EPCs to generate FOXO4(KD)-EPCs and confirmed a successful knockdown. FOXO4(KD)-EPCs gained resistance to apoptosis in response to hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was stronger for the immunodeficient rat ischemic limb tissue than for the rat non-ischemic one. Although the number of apoptotic EPCs injected into the rat ischemic limb was greater than that of apoptotic EPCs injected into the rat non-ischemic limb, FOXO4(KD)-EPCs injected into the rat ischemic limb brought less apoptosis and more neovascularization than EPCs. Taken together, the use of FOXO4(KD)-EPCs with resistance to oxidative stress-induced apoptosis may be a new strategy to augment the effects of therapeutic angiogenesis by intramuscular injection of EPCs. |
format | Online Article Text |
id | pubmed-3963928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39639282014-03-27 FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs Nakayoshi, Takaharu Sasaki, Ken-ichiro Kajimoto, Hidemi Koiwaya, Hiroshi Ohtsuka, Masanori Ueno, Takafumi Chibana, Hidetoshi Itaya, Naoki Sasaki, Masahiro Yokoyama, Shinji Fukumoto, Yoshihiro Imaizumi, Tsutomu PLoS One Research Article The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play a pivotal role in apoptosis signaling of EPCs in response to oxidative stress. Accordingly, we assessed whether FOXO4-knockdown EPCs (FOXO4(KD)-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs. We transfected small interfering RNA targeted against FOXO4 of human EPCs to generate FOXO4(KD)-EPCs and confirmed a successful knockdown. FOXO4(KD)-EPCs gained resistance to apoptosis in response to hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was stronger for the immunodeficient rat ischemic limb tissue than for the rat non-ischemic one. Although the number of apoptotic EPCs injected into the rat ischemic limb was greater than that of apoptotic EPCs injected into the rat non-ischemic limb, FOXO4(KD)-EPCs injected into the rat ischemic limb brought less apoptosis and more neovascularization than EPCs. Taken together, the use of FOXO4(KD)-EPCs with resistance to oxidative stress-induced apoptosis may be a new strategy to augment the effects of therapeutic angiogenesis by intramuscular injection of EPCs. Public Library of Science 2014-03-24 /pmc/articles/PMC3963928/ /pubmed/24663349 http://dx.doi.org/10.1371/journal.pone.0092626 Text en © 2014 Nakayoshi 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 Nakayoshi, Takaharu Sasaki, Ken-ichiro Kajimoto, Hidemi Koiwaya, Hiroshi Ohtsuka, Masanori Ueno, Takafumi Chibana, Hidetoshi Itaya, Naoki Sasaki, Masahiro Yokoyama, Shinji Fukumoto, Yoshihiro Imaizumi, Tsutomu FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs |
title | FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs |
title_full | FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs |
title_fullStr | FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs |
title_full_unstemmed | FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs |
title_short | FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs |
title_sort | foxo4-knockdown suppresses oxidative stress-induced apoptosis of early pro-angiogenic cells and augments their neovascularization capacities in ischemic limbs |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3963928/ https://www.ncbi.nlm.nih.gov/pubmed/24663349 http://dx.doi.org/10.1371/journal.pone.0092626 |
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