Critical role of caveolin-1 in ocular neovascularization and multitargeted antiangiogenic effects of cavtratin via JNK

Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2017-10, Vol.114 (40), p.10737-10742
Main Authors: Jiang, Yida, Lin, Xianchai, Tang, Zhongshu, Lee, Chunsik, Tian, Geng, Du, Yuxiang, Yin, Xiangke, Ren, Xiangrong, Huang, Lijuan, Ye, Zhimin, Chen, Wei, Zhang, Fan, Mi, Jia, Gao, Zhiqin, Wang, Shasha, Chen, Qishan, Xing, Liying, Wang, Bin, Cao, Yihai, Sessa, William C., Ju, Rong, Liu, Yizhi, Li, Xuri
Format: Article
Language:English
Subjects:
Angiogenesis
Antiangiogenics
Biological Sciences
Blindness
Caveolin
Caveolin-1
Clonal deletion
Critical components
Effects
Genetics
JNK protein
Macrophages
Medicin och hälsovetenskap
Microglia
Nitric oxide
Nitric-oxide synthase
Permeability
Platelet-derived growth factor
Proteins
Retina
Vascular endothelial growth factor
Vascular system
Vascularization
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Summary:Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization. Importantly, combined administration of cavtratin and anti–VEGF-A inhibited neovascularization more effectively than monotherapy, suggesting the existence of other pathways inhibited by cavtratin in addition to VEGF-A. Indeed, we found that cavtratin suppressed multiple critical components of pathological angiogenesis, including inflammation, permeability, PDGF-B and endothelial nitric oxide synthase expression (eNOS). Mechanistically, we show that cavtratin inhibits CNV and the survival and migration of microglia and macrophages via JNK. Together, our data demonstrate the unique advantages of cavtratin in antiangiogenic therapy to treat neovascular diseases.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1706394114