A heparin mimetic isolated from a marine shrimp suppresses neovascularization

A heparin mimetic isolated from a marine shrimp suppresses neovascularization

Author Dreyfuss, Juliana Luporini Autor UNIFESP Google Scholar
Regatieri, Caio Vinicius Saito Autor UNIFESP Google Scholar
Lima, M. A. Autor UNIFESP Google Scholar
Paredes-Gamero, E. J. Autor UNIFESP Google Scholar
Brito, A. S. Autor UNIFESP Google Scholar
Chavante, S. F. Google Scholar
Belfort, Rubens Junior Autor UNIFESP Google Scholar
Farah, M. E. Autor UNIFESP Google Scholar
Nader, Helena Bonciani Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Fed Rio Grande do Norte
Abstract 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.
Keywords angiogenesis
endothelial cell
glycosaminoglycans
growth factors
heparin mimetic
proliferation
Language English
Sponsor Fundação 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)
Date 2010-08-01
Published in Journal of Thrombosis and Haemostasis. Malden: Wiley-Blackwell, v. 8, n. 8, p. 1828-1837, 2010.
ISSN 1538-7933 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 1828-1837
Origin http://dx.doi.org/10.1111/j.1538-7836.2010.03916.x
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000280646300022
URI http://repositorio.unifesp.br/handle/11600/32745

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