Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
J Diabetes Res. 2022 Apr 22;2022:1193760. doi: 10.1155/2022/1193760. eCollection 2022.
Pathological neovascularization, which involves a disruption in the balance between angiogenic and antiangiogenic factors under pathological conditions, is the basis of many intraocular diseases. Pigment epithelium-derived factor (PEDF) is a potent natural, endogenous inhibitor of neovascularization because of its antiangiogenic and neuroprotective benefits. However, its application is restricted by its instability and short half-life. The present study is aimed at investigating the cytotoxicity and antiangiogenic effects of PEDF-loaded PEGylated nanoparticles (NP-PEG-PEDF) on high glucose-stimulated human umbilical vein endothelial cells (HUVECs).
In this study, NP-PEG-PEDF were fabricated using the multiple emulsion method for the first time. HUVECs were cultured in a high concentration of glucose (30 mmol/L D-glucose), simulating diabetic conditions. The antiangiogenic effects of vascular endothelial growth factor (VEGF), pure PEDF, and NP-PEG-PEDF on proliferation, migration, and tube formation were evaluated. VEGF secretion in high glucose-stimulated HUVECs was further tested in vitro.
NP-PEG-PEDF exhibited low cytotoxicity in HUVECs. Our results indicated that in vitro, NP-PEG-PEDF attenuated diabetes-induced HUVEC proliferation, migration, and tube formation and suppressed VEGF secretion. The apoptosis of diabetes-induced HUVECs occurred in a dose-dependent manner, which showed a statistically significant difference compared with the PEDF treatment group.
Our study is the first to demonstrate that NP-PEG-PEDF exert antiangiogenic effects on high glucose-stimulated HUVECs and have the potential to alleviate microvascular dysfunction. These data suggest that the NP-PEG-PEDF delivery system may offer an innovative therapeutic strategy for preventing neovascularization of the fundus.
病理性血管新生涉及到在病理条件下血管生成和抗血管生成因子之间平衡的破坏，是许多眼内疾病的基础。色素上皮衍生因子（PEDF）是一种有效的天然内源性血管新生抑制剂，因为它具有抗血管新生和神经保护作用。然而，由于其不稳定性和半衰期短，其应用受到限制。本研究旨在研究载 PEDF 的聚乙二醇化纳米颗粒（NP-PEG-PEDF）对高糖刺激的人脐静脉内皮细胞（HUVEC）的细胞毒性和抗血管生成作用。
本研究首次采用复乳法制备 NP-PEG-PEDF。将 HUVEC 在高浓度葡萄糖（30mmol/L D-葡萄糖）中培养，模拟糖尿病条件。评估血管内皮生长因子（VEGF）、纯 PEDF 和 NP-PEG-PEDF 对增殖、迁移和管形成的抗血管生成作用。进一步在体外测试高糖刺激的 HUVEC 中 VEGF 的分泌。
NP-PEG-PEDF 在 HUVEC 中表现出低细胞毒性。我们的结果表明，在体外，NP-PEG-PEDF 减弱了糖尿病诱导的 HUVEC 增殖、迁移和管形成，并抑制了 VEGF 的分泌。糖尿病诱导的 HUVEC 凋亡呈剂量依赖性，与 PEDF 治疗组相比差异有统计学意义。
本研究首次证明 NP-PEG-PEDF 对高糖刺激的 HUVEC 具有抗血管生成作用，并有可能减轻微血管功能障碍。这些数据表明，NP-PEG-PEDF 给药系统可能为预防眼底新生血管化提供一种创新的治疗策略。
