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VCAM1, HMOX1 and NOS3 differential endothelial expression may impact sickle cell anemia vasculopathy

2021-12-30Journal article Restricted access
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dc.contributor.authorSilva, Marisa
dc.contributor.authorCoelho, Andreia
dc.contributor.authorSofia, Vargas
dc.contributor.authorFaustino, Paula
dc.date.accessioned2022-01-31T15:57:30Z
dc.date.available2022-01-31T15:57:30Z
dc.date.issued2021-12-30
dc.description.abstractEndothelial dysfunction plays a major role in sickle cell anemia (SCA) systemic vasculopathy, with upregulation of adhesion molecules (e.g., VCAM-1), decreased nitric oxide bioavailability, and oxidative stress. We aimed to assess the modulation role of pro-inflammatory and pro-oxidative stimuli on endothelial VCAM1, NOS3, and HMOX1 expression. We also evaluated the effect of the main SCA therapeutic agent, hydroxyurea, on that modulation. Our results showed that two VCAM1 promoter haplotypes, we previously associated with pediatric cerebral vasculopathy and severe hemolysis in SCA, increased promoter activity in TNF-α-stimulated transfected EAhy926 and HBEC cell lines, consistent with a higher VCAM1 expression in macro and microvascular settings. In non-transfected cells, we also observed TNF-α-induced VCAM1 overexpression as well as heme-induced overexpression of HMOX1 in both cell models. Heme did not affect VCAM1 nor NOS3 expression and the latter was also not affected by TNF-α stimulus. Hydroxyurea treatment lowered TNF-induced VCAM1 and NOS3 expression but did not affect heme-induced HMOX1 expression. These data further indicate that VCAM1 haplotypes we studied lead to higher VCAM1 expression affecting not only cerebral but also systemic vasculopathy risk. The differential endothelial expression of VCAM1, NOS3, and HMOX1 also confirms their genetic modulation role in SCA systemic vasculopathy.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBlood Cells Mol Dis. 2022 Mar;93:102639. doi: 10.1016/j.bcmd.2021.102639. Epub 2021 Dec 30.pt_PT
dc.identifier.doihttps://doi.org/10.1016/j.bcmd.2021.102639pt_PT
dc.identifier.issn1079-9796
dc.identifier.urihttp://hdl.handle.net/10400.18/7892
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier/ Academic Presspt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/abs/pii/S1079979621001054?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectSickle Cell Anemiapt_PT
dc.subjectHemept_PT
dc.subjectHydroxyureapt_PT
dc.subjectVascular Endotheliumpt_PT
dc.subjectVCAM1pt_PT
dc.subjectTNF-αpt_PT
dc.subjectVCAM1 Promoter Haplotypespt_PT
dc.subjectHidroxyureapt_PT
dc.subjectAnemia das Células Falciformespt_PT
dc.subjectDoença vascularpt_PT
dc.subjectModificadores genéticospt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectDrepanocitosept_PT
dc.titleVCAM1, HMOX1 and NOS3 differential endothelial expression may impact sickle cell anemia vasculopathypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage102639pt_PT
oaire.citation.titleBlood Cells, Molecules and Diseasespt_PT
oaire.citation.volume93pt_PT
person.familyNameFaustino
person.givenNamePaula
person.identifier.ciencia-idF01A-353A-433E
person.identifier.orcid0000-0002-6269-4867
person.identifier.ridM-3519-2014
person.identifier.scopus-author-id8158641100
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication94303e78-8b7d-4e24-811d-3af3b1a4e330
relation.isAuthorOfPublication.latestForDiscovery94303e78-8b7d-4e24-811d-3af3b1a4e330

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