Use este identificador para citar ou linkar para este item:
https://www.arca.fiocruz.br/handle/icict/14158
HEME CHANGES HIF-α, ENOS AND NITRITE PRODUCTION IN HUVECS AFTER SIMVASTATIN, HU, AND ASCORBIC ACID THERAPIES
Autor(es)
Afiliação
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação 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, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação 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, Brasil
Resumo em Inglês
The 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.
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