Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice

It is of great clinical significance to develop potential novel strategies to prevent cardio-cerebrovascular complications in patients with hyperlipidemia. Vascular Endothelial integrity and function play a key role in the prevention of cardio-cerebrovascular diseases. Endothelial progenitor cells (...

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Autores principales:	Xiao-Hui Dong, Cheng Peng, Yu-Yi Zhang, Yu Jiang, Li-Jun Yang, Jia-Bei He, Xia Tao, Chuan Zhang, Alex F Chen, He-Hui Xie
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	piperlongumine endothelial progenitor cells angiogenesis cerebral ischemic injury hyperlipidemia Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/515b1ff4696e4a9c9fae6c51e262dc01
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spelling	oai:doaj.org-article:515b1ff4696e4a9c9fae6c51e262dc012021-11-15T06:58:58ZLow-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice1663-981210.3389/fphar.2021.689880https://doaj.org/article/515b1ff4696e4a9c9fae6c51e262dc012021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.689880/fullhttps://doaj.org/toc/1663-9812It is of great clinical significance to develop potential novel strategies to prevent cardio-cerebrovascular complications in patients with hyperlipidemia. Vascular Endothelial integrity and function play a key role in the prevention of cardio-cerebrovascular diseases. Endothelial progenitor cells (EPCs) can home to sites of ischemic injury and promote endothelial regeneration and neovascularization. Hypercholesterolemia impairs the function of EPC. The present study attempted to identify the effect of piperlongumine on EPCs’ angiogenic potential and cerebral ischemic injury in high-fat diet-fed (HFD-fed) mice. Here, we showed that treatment with low-does piperlongumine (0.25 mg/kg/day) for 8 weeks significantly improved EPCs function and reduced the cerebral ischemic injury (both infarct volumes and neurobehavioral outcomes) in HFD-fed mice. In addition, low-dose piperlongumine administration increased intracellular NO level and reduced intracellular O2- level in EPCs of HFD-fed mice. Moreover, incubation with piperlongumine (1.0 μM, 24 h) reduced thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) expression levels in EPCs from HFD-fed mice, increased the therapeutic effect of EPC from HFD-fed mice on cerebral ischemic injury reduction and angiogenesis promotion in HFD-fed mice, and the donor derived EPCs homed to the recipient ischemic brain. In conclusion, low-dose piperlongumine can enhance EPCs’ angiogenic potential and protect against cerebral ischemic injury in HFD-fed mice. It is implied that treatment with low-dose piperlongumine might be a potential option to prevent ischemic diseases (including stroke) in patients with hyperlipidemia, and priming with piperlongumine might be a feasible way to improve the efficacy of EPC-based therapy for ischemic diseases.Xiao-Hui DongXiao-Hui DongCheng PengYu-Yi ZhangYu JiangLi-Jun YangJia-Bei HeXia TaoChuan ZhangAlex F ChenHe-Hui XieHe-Hui XieFrontiers Media S.A.articlepiperlongumineendothelial progenitor cellsangiogenesiscerebral ischemic injuryhyperlipidemiaTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	piperlongumine endothelial progenitor cells angiogenesis cerebral ischemic injury hyperlipidemia Therapeutics. Pharmacology RM1-950
spellingShingle	piperlongumine endothelial progenitor cells angiogenesis cerebral ischemic injury hyperlipidemia Therapeutics. Pharmacology RM1-950 Xiao-Hui Dong Xiao-Hui Dong Cheng Peng Yu-Yi Zhang Yu Jiang Li-Jun Yang Jia-Bei He Xia Tao Chuan Zhang Alex F Chen He-Hui Xie He-Hui Xie Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice
description	It is of great clinical significance to develop potential novel strategies to prevent cardio-cerebrovascular complications in patients with hyperlipidemia. Vascular Endothelial integrity and function play a key role in the prevention of cardio-cerebrovascular diseases. Endothelial progenitor cells (EPCs) can home to sites of ischemic injury and promote endothelial regeneration and neovascularization. Hypercholesterolemia impairs the function of EPC. The present study attempted to identify the effect of piperlongumine on EPCs’ angiogenic potential and cerebral ischemic injury in high-fat diet-fed (HFD-fed) mice. Here, we showed that treatment with low-does piperlongumine (0.25 mg/kg/day) for 8 weeks significantly improved EPCs function and reduced the cerebral ischemic injury (both infarct volumes and neurobehavioral outcomes) in HFD-fed mice. In addition, low-dose piperlongumine administration increased intracellular NO level and reduced intracellular O2- level in EPCs of HFD-fed mice. Moreover, incubation with piperlongumine (1.0 μM, 24 h) reduced thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) expression levels in EPCs from HFD-fed mice, increased the therapeutic effect of EPC from HFD-fed mice on cerebral ischemic injury reduction and angiogenesis promotion in HFD-fed mice, and the donor derived EPCs homed to the recipient ischemic brain. In conclusion, low-dose piperlongumine can enhance EPCs’ angiogenic potential and protect against cerebral ischemic injury in HFD-fed mice. It is implied that treatment with low-dose piperlongumine might be a potential option to prevent ischemic diseases (including stroke) in patients with hyperlipidemia, and priming with piperlongumine might be a feasible way to improve the efficacy of EPC-based therapy for ischemic diseases.
format	article
author	Xiao-Hui Dong Xiao-Hui Dong Cheng Peng Yu-Yi Zhang Yu Jiang Li-Jun Yang Jia-Bei He Xia Tao Chuan Zhang Alex F Chen He-Hui Xie He-Hui Xie
author_facet	Xiao-Hui Dong Xiao-Hui Dong Cheng Peng Yu-Yi Zhang Yu Jiang Li-Jun Yang Jia-Bei He Xia Tao Chuan Zhang Alex F Chen He-Hui Xie He-Hui Xie
author_sort	Xiao-Hui Dong
title	Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice
title_short	Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice
title_full	Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice
title_fullStr	Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice
title_full_unstemmed	Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice
title_sort	low-dose piperlongumine rescues impaired function of endothelial progenitor cells and reduces cerebral ischemic injury in high-fat diet-fed mice
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/515b1ff4696e4a9c9fae6c51e262dc01
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Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice

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