Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Oxid Med Cell Longev. 2018 Apr 10;2018:9045976. doi: 10.1155/2018/9045976. eCollection 2018.
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.
内皮祖细胞 (EPCs) 的功能障碍导致糖尿病患者心血管并发症的发生，而白藜芦醇已被证明可以改善 EPC 的功能。硫酸乙酰肝素蛋白聚糖-4 (Synd4) 是一种细胞表面硫酸乙酰肝素蛋白聚糖，已被证明可以促进血管新生。因此，本研究旨在确定白藜芦醇是否通过调节 Synd4 促进 EPC 的血管生成。晚期 EPC 从人外周血中分离出来，并受到 AGE 的刺激。Western blot 表明 AGE 以剂量和时间依赖的方式诱导 Synd4 脱落。NAC 或白藜芦醇部分逆转了 AGE 诱导的 Synd4 脱落，并使 ROS 产生正常化。Synd4 的过表达或白藜芦醇的预处理逆转了 AGE 对 EPC 管形成的损害，并调节了 Akt/eNOS 通路。此外，白藜芦醇通过抑制氧化应激抑制 Synd4 脱落，通过调节 Synd4/Akt/eNOS 通路改善晚期 EPC 的管形成。
