Fibrinolytic activity is associated with presence of cystic medial degeneration in aneurysms of the ascending aorta

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dc.contributor.authorBorges, Luciano F. [UNIFESP]
dc.contributor.authorGomez, Delphine
dc.contributor.authorQuintana, Mercedes
dc.contributor.authorTouat, Ziad
dc.contributor.authorJondeau, Guillaume
dc.contributor.authorLeclercq, Anne
dc.contributor.authorMeilhac, Olivier
dc.contributor.authorJandrot-Perrus, Martine
dc.contributor.authorGutierrez, Paulo S.
dc.contributor.authorFreymuller, Edna [UNIFESP]
dc.contributor.authorVranckx, Roger
dc.contributor.authorMichel, Jean-Baptiste
dc.contributor.institutionUniv Paris 07
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionCtr Reference Syndrome Marfan & Syndromes Apparen
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2016-01-24T14:05:47Z
dc.date.available2016-01-24T14:05:47Z
dc.date.issued2010-12-01
dc.description.abstractFibrinolytic activity is associated with presence of cystic medial degeneration in aneurysms of the ascending aortaAims:Thoracic ascending aortic aneurysms (TAA) are characterized by elastic fibre breakdown and cystic medial degeneration within the aortic media, associated with progressive smooth muscle cell (SMC) rarefaction. the transforming growth factor (TGF)-beta/Smad2 signalling pathway is involved in this process. Because the pericellular fibrinolytic system activation is able to degrade adhesive proteins, activate matrix metalloproteinase (MMP), induce SMC disappearance and increase the bioavailability of TGF-beta, the aim was to investigate the plasminergic system in TAA.Methods and results:Ascending aortas [21 controls and 19 TAAs (of three different aetiologies)] were analysed. Immunohistochemistry showed accumulation of t-PA, u-PA and plasmin in TAAs, associated with residual SMCs. Overexpression of t-PA and u-PA was confirmed by reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting and zymography on TAA extracts and culture medium conditioned by TAA. Plasminogen was present on the SMC surface and inside cytoplasmic vesicles, but plasminogen mRNA was undetectable in the TAA medial layer. Plasmin-antiplasmin complexes were detected in TAA-conditioned medium and activation of the fibrinolytic system was associated with increased fibronectin turnover. Fibronectin-related material was detected immunohistochamically in dense clumps around SMCs and colocalized with latent TGF-beta binding protein-1.Conclusions:The fibrinolytic pathway could play a critical role in TAA progression, via direct or indirect impact on ECM and consecutive modulation of TGF-beta bioavailability.en
dc.description.affiliationUniv Paris 07, INSERM, U698, Paris, France
dc.description.affiliationUniversidade Federal de São Paulo, Ctr Electron Microscopy, São Paulo, Brazil
dc.description.affiliationCtr Reference Syndrome Marfan & Syndromes Apparen, Paris, France
dc.description.affiliationUniv São Paulo, Sch Med, Heart Inst InCor, Pathol Lab, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Ctr Electron Microscopy, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipParis 7 University, France
dc.description.sponsorshipFrench National Research Agency (ANR)
dc.description.sponsorshipSociete Francaise de Cardiologie and Federation Francaise de Cardiologie
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipEuropean Union
dc.description.sponsorshipIDEuropean Union: FP-7-Health-200647
dc.format.extent917-932
dc.identifierhttp://dx.doi.org/10.1111/j.1365-2559.2010.03719.x
dc.identifier.citationHistopathology. Malden: Wiley-Blackwell Publishing, Inc, v. 57, n. 6, p. 917-932, 2010.
dc.identifier.doi10.1111/j.1365-2559.2010.03719.x
dc.identifier.issn0309-0167
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33154
dc.identifier.wosWOS:000285417800014
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofHistopathology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectelectron microscopyen
dc.subjectfibronectinen
dc.subjectLTBP-1en
dc.subjectplasminen
dc.subjectplasminogen activatorsen
dc.subjectsmooth muscle cellsen
dc.subjectTGF-beta 1en
dc.titleFibrinolytic activity is associated with presence of cystic medial degeneration in aneurysms of the ascending aortaen
dc.typeinfo:eu-repo/semantics/article
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