A heparin mimetic isolated from a marine shrimp suppresses neovascularization

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dc.contributor.authorDreyfuss, Juliana Luporini [UNIFESP]
dc.contributor.authorRegatieri, Caio Vinicius Saito [UNIFESP]
dc.contributor.authorLima, M. A. [UNIFESP]
dc.contributor.authorParedes-Gamero, E. J. [UNIFESP]
dc.contributor.authorBrito, A. S. [UNIFESP]
dc.contributor.authorChavante, S. F.
dc.contributor.authorBelfort, Rubens Junior [UNIFESP]
dc.contributor.authorFarah, M. E. [UNIFESP]
dc.contributor.authorNader, Helena Bonciani [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Fed Rio Grande do Norte
dc.date.accessioned2016-01-24T14:05:14Z
dc.date.available2016-01-24T14:05:14Z
dc.date.issued2010-08-01
dc.description.abstractBackground: Choroidal neovascularization (CNV) is the main cause of severe visual loss in age-related macular degeneration (AMD). Heparin/heparan sulfate are known to play important roles in neovascularization due to their abilities to bind and modulate angiogenic growth factors and cytokines. Previously, we have isolated from marine shrimp a heparin-like compound with striking anti-inflammatory action and negligible anticoagulant and hemorrhagic activities. Objectives: To investigate the role of this novel heparin-like compound in angiogenic processes. Methods and Results: the anti-angiogenic effect of this heparinoid in laser-induced CNV and in vitro models is reported. the compound binds to growth factors (FGF-2, EGF and VEGF), blocks endothelial cell proliferation and shows no cytotoxic effect. the decrease in proliferation is not related to cell death either by apoptosis or secondary necrosis. the results also showed that the heparinoid modified the 2-D network organization in capillary-like structures of endothelial cells in Matrigel and reduced the CNV area. the effect on CNV area correlates with decreases in the levels of VEGF and TGF-beta 1 in the choroidal tissue. the low content of 2-O-sulfate groups in this heparinoid may explain its potent anti-angiogenic effect. Conclusions: the properties of the shrimp heparinoid, such as potent anti-angiogenic and anti-inflammatory activities but insignificant anticoagulant or hemorrhagic actions, point to this compound as a compelling drug candidate for treating neovascular AMD and other angioproliferative diseases. A mechanism for the anti-angiogenic effect of the heparinoid is proposed.en
dc.description.affiliationUniversidade Federal de São Paulo, Mol Biol Grad Program, Disciplina Biol Mol, UNIFESP,Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Oftalmol, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Fed Rio Grande do Norte, UFRN, Dept Bioquim, BR-59072970 Natal, RN, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Mol Biol Grad Program, Disciplina Biol Mol, UNIFESP,Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Oftalmol, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent1828-1837
dc.identifierhttp://dx.doi.org/10.1111/j.1538-7836.2010.03916.x
dc.identifier.citationJournal of Thrombosis and Haemostasis. Malden: Wiley-Blackwell, v. 8, n. 8, p. 1828-1837, 2010.
dc.identifier.doi10.1111/j.1538-7836.2010.03916.x
dc.identifier.issn1538-7933
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32745
dc.identifier.wosWOS:000280646300022
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofJournal of Thrombosis and Haemostasis
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectangiogenesisen
dc.subjectendothelial cellen
dc.subjectglycosaminoglycansen
dc.subjectgrowth factorsen
dc.subjectheparin mimeticen
dc.subjectproliferationen
dc.titleA heparin mimetic isolated from a marine shrimp suppresses neovascularizationen
dc.typeinfo:eu-repo/semantics/article
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