A heparin mimetic isolated from a marine shrimp suppresses neovascularization

Detalhes bibliográficos
Autor(a) principal: Dreyfuss, Juliana Luporini [UNIFESP]
Data de Publicação: 2010
Outros Autores: Regatieri, Caio Vinicius Saito [UNIFESP], Lima, M. A. [UNIFESP], Paredes-Gamero, E. J. [UNIFESP], Brito, A. S. [UNIFESP], Chavante, S. F., Belfort, Rubens Junior [UNIFESP], Farah, M. E. [UNIFESP], Nader, Helena Bonciani [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
dARK ID: ark:/48912/001300000vpkh
DOI: 10.1111/j.1538-7836.2010.03916.x
Texto Completo: http://dx.doi.org/10.1111/j.1538-7836.2010.03916.x
http://repositorio.unifesp.br/handle/11600/32745
Resumo: Background: 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.
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spelling A heparin mimetic isolated from a marine shrimp suppresses neovascularizationangiogenesisendothelial cellglycosaminoglycansgrowth factorsheparin mimeticproliferationBackground: 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.Universidade Federal de São Paulo, Mol Biol Grad Program, Disciplina Biol Mol, UNIFESP,Dept Bioquim, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Oftalmol, BR-04044020 São Paulo, BrazilUniv Fed Rio Grande do Norte, UFRN, Dept Bioquim, BR-59072970 Natal, RN, BrazilUniversidade Federal de São Paulo, Mol Biol Grad Program, Disciplina Biol Mol, UNIFESP,Dept Bioquim, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Oftalmol, BR-04044020 São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Wiley-BlackwellUniversidade Federal de São Paulo (UNIFESP)Univ Fed Rio Grande do NorteDreyfuss, Juliana Luporini [UNIFESP]Regatieri, Caio Vinicius Saito [UNIFESP]Lima, M. A. [UNIFESP]Paredes-Gamero, E. J. [UNIFESP]Brito, A. S. [UNIFESP]Chavante, S. F.Belfort, Rubens Junior [UNIFESP]Farah, M. E. [UNIFESP]Nader, Helena Bonciani [UNIFESP]2016-01-24T14:05:14Z2016-01-24T14:05:14Z2010-08-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion1828-1837http://dx.doi.org/10.1111/j.1538-7836.2010.03916.xJournal of Thrombosis and Haemostasis. Malden: Wiley-Blackwell, v. 8, n. 8, p. 1828-1837, 2010.10.1111/j.1538-7836.2010.03916.x1538-7933http://repositorio.unifesp.br/handle/11600/32745WOS:000280646300022ark:/48912/001300000vpkhengJournal of Thrombosis and Haemostasisinfo:eu-repo/semantics/openAccesshttp://olabout.wiley.com/WileyCDA/Section/id-406071.htmlreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2021-09-29T14:54:12Zoai:repositorio.unifesp.br/:11600/32745Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:39:47.682208Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv A heparin mimetic isolated from a marine shrimp suppresses neovascularization
title A heparin mimetic isolated from a marine shrimp suppresses neovascularization
spellingShingle A heparin mimetic isolated from a marine shrimp suppresses neovascularization
A heparin mimetic isolated from a marine shrimp suppresses neovascularization
Dreyfuss, Juliana Luporini [UNIFESP]
angiogenesis
endothelial cell
glycosaminoglycans
growth factors
heparin mimetic
proliferation
Dreyfuss, Juliana Luporini [UNIFESP]
angiogenesis
endothelial cell
glycosaminoglycans
growth factors
heparin mimetic
proliferation
title_short A heparin mimetic isolated from a marine shrimp suppresses neovascularization
title_full A heparin mimetic isolated from a marine shrimp suppresses neovascularization
title_fullStr A heparin mimetic isolated from a marine shrimp suppresses neovascularization
A heparin mimetic isolated from a marine shrimp suppresses neovascularization
title_full_unstemmed A heparin mimetic isolated from a marine shrimp suppresses neovascularization
A heparin mimetic isolated from a marine shrimp suppresses neovascularization
title_sort A heparin mimetic isolated from a marine shrimp suppresses neovascularization
author Dreyfuss, Juliana Luporini [UNIFESP]
author_facet Dreyfuss, Juliana Luporini [UNIFESP]
Dreyfuss, Juliana Luporini [UNIFESP]
Regatieri, Caio Vinicius Saito [UNIFESP]
Lima, M. A. [UNIFESP]
Paredes-Gamero, E. J. [UNIFESP]
Brito, A. S. [UNIFESP]
Chavante, S. F.
Belfort, Rubens Junior [UNIFESP]
Farah, M. E. [UNIFESP]
Nader, Helena Bonciani [UNIFESP]
Regatieri, Caio Vinicius Saito [UNIFESP]
Lima, M. A. [UNIFESP]
Paredes-Gamero, E. J. [UNIFESP]
Brito, A. S. [UNIFESP]
Chavante, S. F.
Belfort, Rubens Junior [UNIFESP]
Farah, M. E. [UNIFESP]
Nader, Helena Bonciani [UNIFESP]
author_role author
author2 Regatieri, Caio Vinicius Saito [UNIFESP]
Lima, M. A. [UNIFESP]
Paredes-Gamero, E. J. [UNIFESP]
Brito, A. S. [UNIFESP]
Chavante, S. F.
Belfort, Rubens Junior [UNIFESP]
Farah, M. E. [UNIFESP]
Nader, Helena Bonciani [UNIFESP]
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
Univ Fed Rio Grande do Norte
dc.contributor.author.fl_str_mv Dreyfuss, Juliana Luporini [UNIFESP]
Regatieri, Caio Vinicius Saito [UNIFESP]
Lima, M. A. [UNIFESP]
Paredes-Gamero, E. J. [UNIFESP]
Brito, A. S. [UNIFESP]
Chavante, S. F.
Belfort, Rubens Junior [UNIFESP]
Farah, M. E. [UNIFESP]
Nader, Helena Bonciani [UNIFESP]
dc.subject.por.fl_str_mv angiogenesis
endothelial cell
glycosaminoglycans
growth factors
heparin mimetic
proliferation
topic angiogenesis
endothelial cell
glycosaminoglycans
growth factors
heparin mimetic
proliferation
description Background: 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.
publishDate 2010
dc.date.none.fl_str_mv 2010-08-01
2016-01-24T14:05:14Z
2016-01-24T14:05:14Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1111/j.1538-7836.2010.03916.x
Journal of Thrombosis and Haemostasis. Malden: Wiley-Blackwell, v. 8, n. 8, p. 1828-1837, 2010.
10.1111/j.1538-7836.2010.03916.x
1538-7933
http://repositorio.unifesp.br/handle/11600/32745
WOS:000280646300022
dc.identifier.dark.fl_str_mv ark:/48912/001300000vpkh
url http://dx.doi.org/10.1111/j.1538-7836.2010.03916.x
http://repositorio.unifesp.br/handle/11600/32745
identifier_str_mv Journal of Thrombosis and Haemostasis. Malden: Wiley-Blackwell, v. 8, n. 8, p. 1828-1837, 2010.
10.1111/j.1538-7836.2010.03916.x
1538-7933
WOS:000280646300022
ark:/48912/001300000vpkh
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Thrombosis and Haemostasis
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
http://olabout.wiley.com/WileyCDA/Section/id-406071.html
eu_rights_str_mv openAccess
rights_invalid_str_mv http://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.format.none.fl_str_mv 1828-1837
dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
_version_ 1822251074979889152
dc.identifier.doi.none.fl_str_mv 10.1111/j.1538-7836.2010.03916.x