A heparin mimetic isolated from a marine shrimp suppresses neovascularization
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , , , |
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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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 |