Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/14158 |
Resumo: | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil |
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Guarda, Caroline Conceição daSantiago, Rayra PereiraPitanga, Thassila NogueiraSantana, Sanzio SilvaZanette, Dalila LucíolaBorges, Valéria de MatosGoncalves, Marilda de Souza2016-05-10T16:03:23Z2016-05-10T16:03:23Z2016GUARDA, C. C. et al. Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies. Microvascular Research, v. 106, p. 128-136, 2016.0026-2862https://www.arca.fiocruz.br/handle/icict/14158dx.doi.org/10.1016/j.mvr.2016.04.002engElsevierHeme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapiesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Salvador, BA, BrasilThe sickle cell disease (SCD) is a hemolytic genetic anemia characterized by free heme and hemoglobin release into intravascular spaces, with endothelial activation. Heme is a proinflammatory molecule able to directly activate vascular endothelium, thus, endothelial dysfunction and vascular disease are major chronic events described in SCD. The aim of this study was to evaluate the production of endothelial nitric oxide synthase (eNOS), nitrite and hypoxia inducible factor alpha (HIF-α) in HUVECs (human umbilical vein endothelial cells) activated by heme in response to simvastatin, hydroxyurea (HU), and ascorbic acid therapies. eNOS and HIF-α production were evaluated by ELISA and nitrite was measured by the Griess technique. The production of HIF-α increased when the cells were stimulated by heme (p b 0.01), while treatment with HU and simvastatin reduced the production (p b 0.01), and treatment with ascorbic acid increased HIF-1a production by the cells (p b 0.01). Hemeincreased eNOS production, (p b 0.01) but showed a heterogeneous pattern, and the lowest concentrations of all the treatments reduced the enzyme production (p b 0.01). The nitrite production by HUVECs was enhanced by stimulation with heme (p b 0.001) andwas reduced by treatment with HU (p b 0.001), ascorbic acid (p b 0.001) and simvastatin (p b 0.01). In summary, our results suggest that the hemolytic vascular microenvironment in SCD requires different therapeutic approaches to promote clinical improvement, and that a combination of therapies may be a viable strategy for treating patients.EndotheliumHemeSimvastatinHydroxyureaAscorbic acidinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/14158/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALGuarda CC Heme changes....pdfGuarda CC Heme changes....pdfapplication/pdf517853https://www.arca.fiocruz.br/bitstream/icict/14158/2/Guarda%20CC%20Heme%20changes....pdf521387a5f13e3781b0af22ec40769e20MD52TEXTGuarda CC Heme changes....pdf.txtGuarda CC Heme changes....pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv |
Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies |
title |
Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies |
spellingShingle |
Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies Guarda, Caroline Conceição da Endothelium Heme Simvastatin Hydroxyurea Ascorbic acid |
title_short |
Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies |
title_full |
Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies |
title_fullStr |
Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies |
title_full_unstemmed |
Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies |
title_sort |
Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies |
author |
Guarda, Caroline Conceição da |
author_facet |
Guarda, Caroline Conceição da Santiago, Rayra Pereira Pitanga, Thassila Nogueira Santana, Sanzio Silva Zanette, Dalila Lucíola Borges, Valéria de Matos Goncalves, Marilda de Souza |
author_role |
author |
author2 |
Santiago, Rayra Pereira Pitanga, Thassila Nogueira Santana, Sanzio Silva Zanette, Dalila Lucíola Borges, Valéria de Matos Goncalves, Marilda de Souza |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Guarda, Caroline Conceição da Santiago, Rayra Pereira Pitanga, Thassila Nogueira Santana, Sanzio Silva Zanette, Dalila Lucíola Borges, Valéria de Matos Goncalves, Marilda de Souza |
dc.subject.en.pt_BR.fl_str_mv |
Endothelium Heme Simvastatin Hydroxyurea Ascorbic acid |
topic |
Endothelium Heme Simvastatin Hydroxyurea Ascorbic acid |
description |
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil |
publishDate |
2016 |
dc.date.accessioned.fl_str_mv |
2016-05-10T16:03:23Z |
dc.date.available.fl_str_mv |
2016-05-10T16:03:23Z |
dc.date.issued.fl_str_mv |
2016 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
GUARDA, C. C. et al. Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies. Microvascular Research, v. 106, p. 128-136, 2016. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/14158 |
dc.identifier.issn.none.fl_str_mv |
0026-2862 |
dc.identifier.doi.none.fl_str_mv |
dx.doi.org/10.1016/j.mvr.2016.04.002 |
identifier_str_mv |
GUARDA, C. C. et al. Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies. Microvascular Research, v. 106, p. 128-136, 2016. 0026-2862 dx.doi.org/10.1016/j.mvr.2016.04.002 |
url |
https://www.arca.fiocruz.br/handle/icict/14158 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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