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学科主题: 临床医学
题名:
Anti-Angiogenic Effects of a Mutant Endostatin: A New Prospect for Treating Retinal and Choroidal Neovascularization
作者: Bai, Yujing1; Zhao, Min1; Zhang, Chunfang2; Li, Shanshan1; Qi, Yun1; Wang, Bin1; Huang, Lvzhen1; Li, Xiaoxin1
刊名: PLOS ONE
发表日期: 2014-11-07
DOI: 10.1371/journal.pone.0112448
卷: 9, 期:11
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: ENDOTHELIAL GROWTH-FACTOR ; MACULAR DEGENERATION ; POLYETHYLENE-GLYCOL ; OCULAR NEOVASCULARIZATION ; THERAPY ; FRAGMENTS ; DELIVERY ; EYE
英文摘要:

Purpose: Pathological fundus angiogenesis is a major cause of vision loss in retina diseases. Endostatin, a C-terminal fragment of collagen XVIII, is an endogenous anti-angiogenic protein. The present study aimed to investigate the in vitro and in vivo anti-angiogenic properties of two proteins: an N-terminal H1D/H3D mutant endostatin (M-ES) and a polyethylene glycol propionaldehyde (PEG) covalent M-ES (PEG-M-ES).

Methods: M-ES and PEG-M-ES properties were characterized in vitro using a zinc ion binding assay and a stability test. Activity assays, including migration, proliferation, and tube formation assays, were performed with human retinal microvascular endothelial cells (HRMECs) and human umbilical vein endothelial cells (HUVECs). Mouse oxygen-induced retinopathy (OIR) and choroidal neovascularization (CNV) models were used to evaluate in vivo anti-angiogenic effects. In addition, a rabbit model was used to study the retinal pharmacokinetic profile following an intravitreal injection.

Results: The results indicated that the H1D/H3D mutations of endostatin reduced the zinc binding capacity of M-ES and facilitated PEG covalent binding. PEG-M-ES was more stable and persisted longer in the retina compared with M-ES. The in vitro studies demonstrated that M-ES and PEG-M-ES inhibited HRMEC and HUVEC proliferation, migration, and tube formation more efficiently than ES. In vivo, a single intravitreal injection of M-ES and PEG-M-ES significantly decreased neovascularization in both the OIR and CNV animal models.

Conclusion: The present study demonstrated for the first time that PEG-M-ES exhibits a long-term inhibitory effect on neovascularization in vitro and in vivo. These data suggest that PEG-M-ES may represent an innovative therapeutic strategy to prevent fundus neovascularization.

语种: 英语
所属项目编号: 2011CB510200 ; Z131102000413004 ; 81200690
项目资助者: National Basic Research Program of China [973 Program] ; Beijing Nova Program ; National Natural Science Foundation of China
WOS记录号: WOS:000344863100096
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53144
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Beijing 100871, Peoples R China
2.Peking Univ, Peoples Hosp, Dept Ophthalmol,Key Lab Vis Loss & Restorat,Minis, Beijing Key Lab Diag & Treatment Retinal & Choroi, Beijing 100871, Peoples R China

Recommended Citation:
Bai, Yujing,Zhao, Min,Zhang, Chunfang,et al. Anti-Angiogenic Effects of a Mutant Endostatin: A New Prospect for Treating Retinal and Choroidal Neovascularization[J]. PLOS ONE,2014,9(11).
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