Abstract:
:Hypoxia-inducible factor (HIF) signaling cascade plays a critical role in angiogenesis by activating the transcription of genes encoding angiogenic growth factors. This study evaluated the effects of YC-1, a HIF-1 inhibitor, on the morphological, biochemical and molecular changes in human retinal microvascular endothelial cells. We found that YC-1 suppressed vascular endothelial cell proliferation, migration and tube formation, while it significantly increased the proteasome activity. Moreover, YC-1 induced a G(0)/G(1) cell-cycle arrest, whereas it exerted only an insignificant proapoptotic effects. Under normoxia or hypoxia, YC-1 did not alter the morphology or the cell viability. Additionally, under hypoxic conditions, YC-1 downregulated HIF-2alpha, VEGF, EPO, ET-1, and MMP-9 mRNA and protein levels, this was accompanied by a significant decrease in the MMP-9 activity. YC-1 decreased the basal expression of HIF-1alpha protein under normoxia, whereas it inhibited HIF-1alpha protein synthesis, stability, and nuclear translocation mechanisms under hypoxia. Furthermore, in a 3D collagen matrix model using mouse retinal explants cultured under normoxic and hypoxic conditions, YC-1; (1) inhibited outgrowth of new vessel sprouts; (2) reduced VEGF expression; (3) dramatically decreased the vessels immunoreactivities for CD31 and von Willebrand Factor (vWF); and (4) was highly effective in reducing the vascular density within the retina, compared to controls. These findings indicate that YC-1 possesses several antiangiogenic properties, both in vitro and ex vivo, which could be exploited as valuable therapeutic potentials to inhibit formation and the growth of new retinal vessels in the hypoxic retina.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
DeNiro M,Alsmadi O,Al-Mohanna Fdoi
10.1016/j.exer.2009.06.013subject
Has Abstractpub_date
2009-11-01 00:00:00pages
700-17issue
5eissn
0014-4835issn
1096-0007pii
S0014-4835(09)00185-7journal_volume
89pub_type
杂志文章abstract::The heparan sulfate (HS) is a component of proteoglycans in the extracellular matrix and on cell surfaces, modulating developmental processes. The aim of this study is to investigate whether the defect of HS in the periocular mesenchyme impairs ocular morphogenesis. First, using Protein 0-Cre transgenic mice, we ablat...
journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
pub_type: 杂志文章
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doi:10.1016/j.exer.2016.02.002
更新日期:2016-04-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
pub_type: 杂志文章,评审
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2013.12.015
更新日期:2014-03-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(91)90160-g
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journal_title:Experimental eye research
pub_type: 杂志文章
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2010.05.017
更新日期:2010-08-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
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更新日期:1997-12-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2009.05.002
更新日期:2009-11-01 00:00:00
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pub_type: 杂志文章
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journal_title:Experimental eye research
pub_type: 杂志文章
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更新日期:2018-10-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
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