Department of Ophthalmology, Sichuan Academy of Medical Sciences, Sichuan, China.
Adv Exp Med Biol. 2010;664:341-7. doi: 10.1007/978-1-4419-1399-9_39.
To investigate protamine sulfate inhibition of expression of the vascular endothelial growth factor (VEGF) and VEGF-VEGFR binding in vitro and to find a new drug that inhibits neovascularization, which can potentially be used to treat angiogenic eye diseases such as diabetic retinopathy and age-related macular degeneration (AMD).
Monkey retinal vascular endothelial cells (RF/6A) were cultured in vitro and different concentrations of protamine sulfate were added to the vascular endothelial cells after three passages. VEGF expression level was examined by ELISA and immunohistochemistry after the cells were treated with protamine sulfate.
VEGF expression decreased in a dose-dependent pattern in 10-80 mug/ml of protamine sulfate. We also found that protamine sulfate could inhibit VEGF to bind to its receptor, VEGFR.
Protamine sulfate could inhibit VEGF expression and VEGF-VEGFR binding in vitro. Protamine sulfate may be used for inhibiting neovascularization in angiogenic eye diseases. Angiogenic eye diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion are the main blindness-causing diseases. Previous studies indicated that VEGF and its receptor were involved in the pathogenesis, development and prognosis of these diseases. VEGF inhibition drugs have been used successfully in clinical treatment, but the cost is prohibitive.Protamine sulfate is a common, inexpensive anti-coagulation drug widely used for anti-coagulation in cases when heparin has been overused in the clinic. Recent studies suggest that protamine sulfate can inhibit tumor growth, probably through inhibiting vascular growth of the tumor. In this study we showed that protamine sulfate could inhibit VEGF and the binding of VEGF and its receptor, implying that protamine sulfate may inhibit blood vessel growth through inhibition of the VEGF pathway. This study further suggested that protamine sulfate may be potentially used to treat angiogenic eye diseases.
研究硫酸鱼精蛋白体外抑制血管内皮生长因子（VEGF）表达及其与 VEGFR 结合的作用，寻找一种新的抗血管生成药物，用于治疗糖尿病视网膜病变和年龄相关性黄斑变性（AMD）等血管生成性眼病。
体外培养猴视网膜血管内皮细胞（RF/6A），传代 3 代后加入不同浓度的硫酸鱼精蛋白，酶联免疫吸附试验（ELISA）和免疫组化检测硫酸鱼精蛋白处理后血管内皮细胞 VEGF 表达水平。
10~80μg/ml 硫酸鱼精蛋白呈剂量依赖性降低 VEGF 表达，且能抑制 VEGF 与 VEGFR 结合。
硫酸鱼精蛋白体外能抑制 VEGF 表达及其与 VEGFR 结合，可能用于抑制血管生成性眼病的新生血管形成。糖尿病视网膜病变（DR）、年龄相关性黄斑变性（AMD）和视网膜静脉阻塞等血管生成性眼病是主要致盲眼病。既往研究表明 VEGF 及其受体参与这些疾病的发病、发展和预后，VEGF 抑制药物已成功用于临床治疗，但费用昂贵。硫酸鱼精蛋白是一种常用、廉价的抗凝药物，广泛用于肝素在临床上超适应证使用的抗凝。最近的研究表明，硫酸鱼精蛋白可通过抑制肿瘤血管生长而抑制肿瘤生长。本研究显示硫酸鱼精蛋白能抑制 VEGF 及其与 VEGFR 结合，提示硫酸鱼精蛋白可能通过抑制 VEGF 通路抑制血管生长，进一步提示硫酸鱼精蛋白可能用于治疗血管生成性眼病。
