Resveratrol Improves Tube Formation in AGE-Induced Late Endothelial Progenitor Cells by Suppressing Syndecan-4 Shedding.

Resveratrol Improves Tube Formation in AGE-Induced Late Endothelial Progenitor Cells by Suppressing Syndecan-4 Shedding.
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白藜芦醇通过抑制 Syndecan-4 脱落来改善 AGE 诱导的晚期内皮祖细胞的管形成。

DOI:
10.1155/2018/9045976
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发表时间:
2018
影响因子:
--
通讯作者:
Xu B
Xu B
中科院分区:
生物学2区
文献类型:
--
作者:
Wu H;Chen Z;Chen JZ;Xie J;Xu B

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内皮祖细胞(EPCs)功能障碍与糖尿病心血管并发症有关,白藜芦醇已被证明可改善EPCs功能。Syndecan-4 (Synd4)是一种细胞表面硫酸肝素蛋白多糖,已被证明可以促进新生血管的形成。因此,本研究旨在确定白藜芦醇是否通过调节Synd4促进EPCs的血管生成。从人外周血中分离晚期EPCs,用AGEs刺激。Western blot结果显示,AGEs诱导Synd4脱落呈剂量依赖性和时间依赖性。NAC或白藜芦醇可以部分逆转年龄诱导的Synd4脱落,同时使ROS产生正常化。过表达Synd4或预处理白藜芦醇可逆转age损伤的EPCs小管形成,并调节Akt/eNOS通路。此外,白藜芦醇通过抑制氧化应激抑制Synd4的脱落,并通过调节Synd4/Akt/eNOS通路改善晚期EPCs的管状形成。
Dysfunction of endothelial progenitor cells (EPCs) contributes to cardiovascular complications in diabetes, and resveratrol has been shown to improve EPC functions. Syndecan-4 (Synd4), a cell surface heparin sulfate proteoglycan, has been shown to promote neovascularization. Thus, the present study was performed to determine whether resveratrol promoted angiogenesis of EPCs by regulating Synd4. Late EPCs were isolated from human peripheral blood and stimulated with AGEs. Western blot showed that AGEs induced Synd4 shedding in a dose- and time-dependent manner. AGE-induced Synd4 shedding was partly reversed by NAC or resveratrol, along with normalized ROS production. Overexpression of Synd4 or pretreatment of resveratrol reversed AGE-impaired tube formation of EPCs and regulated the Akt/eNOS pathway. Furthermore, resveratrol suppressed Synd4 shedding via the inhibition of oxidative stress and improved tube formation of late EPCs via the regulation of the Synd4/Akt/eNOS pathway.
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