Resveratrol promotes angiogenesis in a foxo1-dependent manner in hind limb ischemia in mice

Dongxiao Fan; Chenshu Liu; Zeling Guo; Kan Huang; Meixiu Peng; Na Li; Hengli Luo; Tengyao Wang; Zhipeng Cen; Weikang Cai; Lei Gu; Sifan Chen; Zilun Li

doi:10.3390/molecules26247528

Resveratrol promotes angiogenesis in a foxo1-dependent manner in hind limb ischemia in mice

Dongxiao Fan, Chenshu Liu, Zeling Guo, Kan Huang, Meixiu Peng, Na Li, Hengli Luo, Tengyao Wang, Zhipeng Cen, Weikang Cai, Lei Gu, Sifan Chen, Zilun Li

Molecular and Cellular Biochemistry

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

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.

Original language	English
Article number	7528
Journal	Molecules
Volume	26
Issue number	24
DOIs	https://doi.org/10.3390/molecules26247528
State	Published - Dec 1 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Funding

This work was supported by grants from: 1. National Natural Science Foundation of China (No. 81670439, No. 81970406); 2. Guangdong Basic and Applied Basic Research Foundation (No. 2021B1515020005); 3. Young Scientists Fund of the National Natural Science Foundation of China (No. 81900757); 4. Fundamental Research Funds for the Central Universities (No. 20ykzd11); 5. Guangdong Science and Technology Department (2020B1212060018, 2020B1212030004). Funding: This work was supported by grants from: 1. National Natural Science Foundation of China (No. 81670439, No. 81970406); 2. Guangdong Basic and Applied Basic Research Foundation (No. 2021B1515020005); 3. Young Scientists Fund of the National Natural Science Foundation of China (No. 81900757); 4. Fundamental Research Funds for the Central Universities (No. 20ykzd11); 5. Guangdong Science and Technology Department (2020B1212060018, 2020B1212030004).

Funders	Funder number
Basic and Applied Basic Research Foundation of Guangdong Province	81900757, 2021B1515020005
National Natural Science Foundation of China (NSFC)	81670439, 81970406
Guangdong Science and Technology Department	2020B1212030004, 2020B1212060018
Fundamental Research Funds for the Central Universities	20ykzd11

Keywords

FoxO1
Hind limb ischemia
Metabolomics
Resveratrol
Therapeutic angiogenesis

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/molecules26247528

Cite this

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title = "Resveratrol promotes angiogenesis in a foxo1-dependent manner in hind limb ischemia in mice",

abstract = "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.",

keywords = "FoxO1, Hind limb ischemia, Metabolomics, Resveratrol, Therapeutic angiogenesis",

author = "Dongxiao Fan and Chenshu Liu and Zeling Guo and Kan Huang and Meixiu Peng and Na Li and Hengli Luo and Tengyao Wang and Zhipeng Cen and Weikang Cai and Lei Gu and Sifan Chen and Zilun Li",

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AU - Fan, Dongxiao

AU - Liu, Chenshu

AU - Guo, Zeling

AU - Huang, Kan

AU - Peng, Meixiu

AU - Li, Na

AU - Luo, Hengli

AU - Wang, Tengyao

AU - Cen, Zhipeng

AU - Cai, Weikang

AU - Gu, Lei

AU - Chen, Sifan

AU - Li, Zilun

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AB - 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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Resveratrol promotes angiogenesis in a foxo1-dependent manner in hind limb ischemia in mice

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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