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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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