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Transthyretin proteins regulate angiogenesis by conferring different molecular identities to endothelial cells

2013Journal article Open access
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dc.contributor.authorNunes, Raquel J.
dc.contributor.authorde Oliveira, Paula
dc.contributor.authorLages, Ana
dc.contributor.authorBecker, Jörg D.
dc.contributor.authorMarcelino, Paulo
dc.contributor.authorBarroso, Eduardo
dc.contributor.authorPerdigoto, Rui
dc.contributor.authorKelly, Jeffery W.
dc.contributor.authorQuintas, Alexandre
dc.contributor.authorSantos, Susana Constantino Rosa
dc.date.accessioned2021-12-21T16:50:07Z
dc.date.available2021-12-21T16:50:07Z
dc.date.issued2013
dc.description© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.pt_PT
dc.description.abstractFamilial amyloidotic polyneuropathy (FAP) has a high prevalence in Portugal, and the most common form of hereditary amyloidosis is caused by an amyloidogenic variant of transthyretin (TTR) with a substitution of methionine for valine at position 30 (V30M). Until now, the available efficient therapy is liver transplantation, when performed in an early phase of the onset of the disease symptoms. However, transplanted FAP patients have a significantly higher incidence of early hepatic artery thrombosis compared with non-FAP transplanted patients. Because FAP was described as an independent risk factor for early hepatic artery thrombosis, more studies to understand the underlying mechanisms involved in this outcome are of the utmost importance. Knowing that the liver is the major site for TTR production, we investigated the biological effects of TTR proteins in the vasculature and on angiogenesis. In this study, we identified genes differentially expressed in endothelial cells exposed to the WT or V30M tetramer. We found that endothelial cells may acquire different molecular identities when exposed to these proteins, and consequently TTR could regulate angiogenesis. Moreover, we show that V30M decreases endothelial survival by inducing apoptosis, and it inhibits migration. These findings provide new knowledge that may have critical implications in the prevention of early hepatic artery thrombosis in FAP patients after liver transplantation.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciencia e Tecnologia Grant PIC/IC/83062/2007. Supported by Fundação para a Ciencia e Tecnologia (FCT) Fellowship SFRH/BPD/43482/2008.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Biol Chem. 2013 Nov 1;288(44):31752-60pt_PT
dc.identifier.doi10.1074/jbc.M113.469858pt_PT
dc.identifier.eissn1083-351X
dc.identifier.issn0021-9258
dc.identifier.urihttp://hdl.handle.net/10451/50507
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/journal-of-biological-chemistrypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAngiogenesispt_PT
dc.subjectEndothelial Cellpt_PT
dc.subjectFamilial Amyloidotic Polyneuropathypt_PT
dc.subjectGene Expressionpt_PT
dc.subjectMicroarraypt_PT
dc.subjectTransthyretinpt_PT
dc.subjectVascular Biologypt_PT
dc.titleTransthyretin proteins regulate angiogenesis by conferring different molecular identities to endothelial cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5646-ICCMS/PIC%2FIC%2F83062%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F43482%2F2008/PT
oaire.citation.endPage31760pt_PT
oaire.citation.issue44pt_PT
oaire.citation.startPage31752pt_PT
oaire.citation.titleJournal of Biological Chemistrypt_PT
oaire.citation.volume288pt_PT
oaire.fundingStream5646-ICCMS
oaire.fundingStreamSFRH
person.familyNameConstantino Rosa Santos
person.givenNameSusana
person.identifier1814324
person.identifier.ciencia-idF11D-8C75-78BF
person.identifier.orcid0000-0002-5711-1292
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isProjectOfPublication441a2abc-4f23-4f64-b72d-7479c382229d
relation.isProjectOfPublication38904d90-c701-499b-a98c-138c3757bfcb
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