Resveratrol Promotes Angiogenesis in a FoxO1-Dependent Manner in Hind Limb Ischemia in Mice

Molecules

Weikang Cai¹  Zeling Guo²  Zilun Li³  Dongxiao Fan³  Kan Huang³  Na Li³  Chenshu Liu³  Zhipeng Cen⁴  Hengli Luo⁴  Tengyao Wang⁴  Sifan Chen⁴  Lei Gu⁵  Meixiu Peng⁶ 

[1]Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine, Old Westbury, NY 11568, USA

[2]Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China

[3]Division of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China

[4]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China

[5]Max Planck Institute for Heart and Lung Research and Cardiopulmonary Institute (CPI), 61231 Bad Nauheim, Germany

[6]National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China

关键词: hind limb ischemia;    therapeutic angiogenesis;    resveratrol;    FoxO1;    metabolomics;   

DOI  :  10.3390/molecules26247528

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown