Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies

Detalhes bibliográficos
Autor(a) principal: Guarda, Caroline Conceição da
Data de Publicação: 2016
Outros Autores: Santiago, Rayra Pereira, Pitanga, Thassila Nogueira, Santana, Sanzio Silva, Zanette, Dalila Lucíola, Borges, Valéria de Matos, Goncalves, Marilda de Souza
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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spelling 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
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
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