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Resveratrol Promotes Angiogenesis in a FoxO1-Dependent Manner in Hind Limb Ischemia in Mice
Critical limb ischemia (CLI) is a severe form of peripheral artery diseases (PAD) and seriously endangers the health of people. Therapeutic angiogenesis represents an important treatment strategy for CLI; various methods have been applied to enhance collateral circulation. However, the current devel...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707225/ https://www.ncbi.nlm.nih.gov/pubmed/34946610 http://dx.doi.org/10.3390/molecules26247528 |
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author | Fan, Dongxiao Liu, Chenshu Guo, Zeling Huang, Kan Peng, Meixiu Li, Na Luo, Hengli Wang, Tengyao Cen, Zhipeng Cai, Weikang Gu, Lei Chen, Sifan Li, Zilun |
author_facet | Fan, Dongxiao Liu, Chenshu Guo, Zeling Huang, Kan Peng, Meixiu Li, Na Luo, Hengli Wang, Tengyao Cen, Zhipeng Cai, Weikang Gu, Lei Chen, Sifan Li, Zilun |
author_sort | Fan, Dongxiao |
collection | PubMed |
description | Critical limb ischemia (CLI) is a severe form of peripheral artery diseases (PAD) and seriously endangers the health of people. Therapeutic angiogenesis represents an important treatment strategy for CLI; various methods have been applied to enhance collateral circulation. However, the current development drug therapy to promote angiogenesis is limited. Resveratrol (RSV), a polyphenol compound extracted from plants, has various properties such as anti-oxidative, anti-inflammatory and anti-cancer effects. Whether RSV exerts protective effects on CLI remains elusive. In the current study, we demonstrated that oral intake of RSV significantly improved hind limb ischemia in mice, and increased the expression of phosphorylated Forkhead box class-O1 (FoxO1). RSV treatment in human umbilical vein endothelial cells (HUVECs) could increase the phosphorylation of FoxO1 and its cytoplasmic re-localization to promote angiogenesis. Then we manipulated FoxO1 in HUVECs to further verify that the effect of RSV on angiogenesis is in a FoxO1-dependent manner. Furthermore, we performed metabolomics to screen the metabolic pathways altered upon RSV intervention. We found that the pathways of pyrimidine metabolism, purine metabolism, as well as alanine, aspartate and glutamate metabolism, were highly correlated with the beneficial effects of RSV on the ischemic muscle. This study provides a novel direction for the medical therapy to CLI. |
format | Online Article Text |
id | pubmed-8707225 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87072252021-12-25 Resveratrol Promotes Angiogenesis in a FoxO1-Dependent Manner in Hind Limb Ischemia in Mice Fan, Dongxiao Liu, Chenshu Guo, Zeling Huang, Kan Peng, Meixiu Li, Na Luo, Hengli Wang, Tengyao Cen, Zhipeng Cai, Weikang Gu, Lei Chen, Sifan Li, Zilun Molecules Article Critical limb ischemia (CLI) is a severe form of peripheral artery diseases (PAD) and seriously endangers the health of people. Therapeutic angiogenesis represents an important treatment strategy for CLI; various methods have been applied to enhance collateral circulation. However, the current development drug therapy to promote angiogenesis is limited. Resveratrol (RSV), a polyphenol compound extracted from plants, has various properties such as anti-oxidative, anti-inflammatory and anti-cancer effects. Whether RSV exerts protective effects on CLI remains elusive. In the current study, we demonstrated that oral intake of RSV significantly improved hind limb ischemia in mice, and increased the expression of phosphorylated Forkhead box class-O1 (FoxO1). RSV treatment in human umbilical vein endothelial cells (HUVECs) could increase the phosphorylation of FoxO1 and its cytoplasmic re-localization to promote angiogenesis. Then we manipulated FoxO1 in HUVECs to further verify that the effect of RSV on angiogenesis is in a FoxO1-dependent manner. Furthermore, we performed metabolomics to screen the metabolic pathways altered upon RSV intervention. We found that the pathways of pyrimidine metabolism, purine metabolism, as well as alanine, aspartate and glutamate metabolism, were highly correlated with the beneficial effects of RSV on the ischemic muscle. This study provides a novel direction for the medical therapy to CLI. MDPI 2021-12-12 /pmc/articles/PMC8707225/ /pubmed/34946610 http://dx.doi.org/10.3390/molecules26247528 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fan, Dongxiao Liu, Chenshu Guo, Zeling Huang, Kan Peng, Meixiu Li, Na Luo, Hengli Wang, Tengyao Cen, Zhipeng Cai, Weikang Gu, Lei Chen, Sifan Li, Zilun Resveratrol Promotes Angiogenesis in a FoxO1-Dependent Manner in Hind Limb Ischemia in Mice |
title | Resveratrol Promotes Angiogenesis in a FoxO1-Dependent Manner in Hind Limb Ischemia in Mice |
title_full | Resveratrol Promotes Angiogenesis in a FoxO1-Dependent Manner in Hind Limb Ischemia in Mice |
title_fullStr | Resveratrol Promotes Angiogenesis in a FoxO1-Dependent Manner in Hind Limb Ischemia in Mice |
title_full_unstemmed | Resveratrol Promotes Angiogenesis in a FoxO1-Dependent Manner in Hind Limb Ischemia in Mice |
title_short | Resveratrol Promotes Angiogenesis in a FoxO1-Dependent Manner in Hind Limb Ischemia in Mice |
title_sort | resveratrol promotes angiogenesis in a foxo1-dependent manner in hind limb ischemia in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707225/ https://www.ncbi.nlm.nih.gov/pubmed/34946610 http://dx.doi.org/10.3390/molecules26247528 |
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