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Heparanase and vascular endothelial growth factor expression is increased in hypoxia-induced retinal neovascularization

Hu, Jie; Song, Xin; He, Yi Qing; Freeman, Craig; Yuan, Ling; Yu, HongHua; Tang, Shibo; Parish, Christopher

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PURPOSE. Heparanase and VEGF are related closely to angiogenesis in cancer. The purpose of our study was to evaluate the expression and correlation of heparanase and VEGF in hypoxia-induced retinal neovascularization. METHODS. C57BL/6 oxygen-induced retinopathy (OIR) mice and human retinal microvascular endothelial cells (HRECs) were treated with the hypoxia mimetic agent cobalt chloride (CoCl2), and in the presence of the heparanase inhibitor phosphomannopentaose sulfate (Muparfostat, PI-88)....[Show more]

dc.contributor.authorHu, Jie
dc.contributor.authorSong, Xin
dc.contributor.authorHe, Yi Qing
dc.contributor.authorFreeman, Craig
dc.contributor.authorYuan, Ling
dc.contributor.authorYu, HongHua
dc.contributor.authorTang, Shibo
dc.contributor.authorParish, Christopher
dc.date.accessioned2015-12-13T22:19:42Z
dc.identifier.issn1552-5783
dc.identifier.urihttp://hdl.handle.net/1885/71953
dc.description.abstractPURPOSE. Heparanase and VEGF are related closely to angiogenesis in cancer. The purpose of our study was to evaluate the expression and correlation of heparanase and VEGF in hypoxia-induced retinal neovascularization. METHODS. C57BL/6 oxygen-induced retinopathy (OIR) mice and human retinal microvascular endothelial cells (HRECs) were treated with the hypoxia mimetic agent cobalt chloride (CoCl2), and in the presence of the heparanase inhibitor phosphomannopentaose sulfate (Muparfostat, PI-88). Heparanase activity was assayed in HRECs, and the expression of heparanase, VEGF protein and mRNA were evaluated by immunofluorescence, ELISA, Western blot, and real-time PCR while retinal flat mounts were used to evaluate the area of neovascularization of mice retina. RESULTS. HREC heparanase activity was increased by treatment with CoCl2, but was decreased by PI-88. Immunofluorescence showed that heparanase and VEGF staining was intense in hypoxia-treated HRECs and OIR mice retina, while VEGF staining was faint in the normoxia and PI-88-treated ones. Western blot and real-time PCR results indicated that the expression of heparanase and VEGF was increased under hypoxic conditions, and the increase of VEGF was inhibited by PI-88. Retinal flat mounts showed that the area of new vessels in retina of OIR mice was increased compared to the normoxic mice, and this effect was inhibited by PI-88. CONCLUSIONS. Heparanase is upregulated and associated with the VEGF expression in hypoxia-induced retinal diseases. Heparanase is involved in hypoxia-induced neovascularization through promoting VEGF expression and may be a new therapeutic target for hypoxia-induced neovascularization retinal diseases.
dc.publisherAssociation for Research in Vision and Opthalmology
dc.rightsAuthor/s retain copyright
dc.sourceInvestigative Ophthalmology and Visual Science
dc.subjectKeywords: cobalt chloride; heparanase; pi 88; vasculotropin; beta glucuronidase; heparanase; RNA; vasculotropin A; animal experiment; animal model; animal tissue; article; confocal microscopy; controlled study; enzyme activity; enzyme linked immunosorbent assay; hu
dc.titleHeparanase and vascular endothelial growth factor expression is increased in hypoxia-induced retinal neovascularization
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume53
dc.date.issued2012
local.identifier.absfor110399 - Clinical Sciences not elsewhere classified
local.identifier.ariespublicationf5625xPUB2972
local.type.statusPublished Version
local.contributor.affiliationHu, Jie, Sun Yat-sen University
local.contributor.affiliationSong, Xin, Sun Yat-sen University
local.contributor.affiliationHe, Yi Qing, Sun Yat-sen University
local.contributor.affiliationFreeman, Craig, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationParish, Christopher, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationYuan, Ling, Zhongshan Ophthalmic center of Sun Yat-sen University
local.contributor.affiliationYu , HongHua , Zhongshan Ophthalmic center of Sun Yat-sen University
local.contributor.affiliationTang , Shibo, Zhongshan Ophthalmic center of Sun Yat-sen University
local.bibliographicCitation.issue11
local.bibliographicCitation.startpage6810
local.bibliographicCitation.lastpage6817
local.identifier.doi10.1167/iovs.11-9144
local.identifier.absseo920104 - Diabetes
dc.date.updated2016-02-24T09:04:26Z
local.identifier.scopusID2-s2.0-84871886241
local.identifier.thomsonID000310589900010
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

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