Rheumatic Heart Disease and Myxomatous Degeneration: Differences and Similarities of Valve Damage Resulting from Autoimmune Reactions and Matrix Disorganization

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorMARTINS, Carlo de Oliveira
dc.contributor.authorDEMARCHI, Lea
dc.contributor.authorFERREIRA, Frederico Moraes
dc.contributor.authorPOMERANTZEFF, Pablo Maria Alberto
dc.contributor.authorBRANDAO, Carlos
dc.contributor.authorSAMPAIO, Roney Orismar
dc.contributor.authorSPINA, Guilherme Sobreira
dc.contributor.authorKALIL, Jorge
dc.contributor.authorCUNHA-NETO, Edecio
dc.contributor.authorGUILHERME, Luiza
dc.date.accessioned2017-04-07T15:05:17Z
dc.date.available2017-04-07T15:05:17Z
dc.date.issued2017
dc.description.abstractAutoimmune inflammatory reactions leading to rheumatic fever (RF) and rheumatic heart disease (RHD) result from untreated Streptococcus pyogenes throat infections in individuals who exhibit genetic susceptibility. Immune effector mechanisms have been described that lead to heart tissue damage culminating in mitral and aortic valve dysfunctions. In myxomatous valve degeneration (MXD), the mitral valve is also damaged due to non-inflammatory mechanisms. Both diseases are characterized by structural valve disarray and a previous proteomic analysis of them has disclosed a distinct profile of matrix/structural proteins differentially expressed. Given their relevance in organizing valve tissue, we quantitatively evaluated the expression of vimentin, collagen VI, lumican, and vitronectin as well as performed immunohistochemical analysis of their distribution in valve tissue lesions of patients in both diseases. We identified abundant expression of two isoforms of vimentin (45 kDa, 42 kDa) with reduced expression of the full-size protein (54 kDa) in RHD valves. We also found increased vitronectin expression, reduced collagen VI expression and similar lumican expression between RHD and MXD valves. Immunohistochemical analysis indicated disrupted patterns of these proteins in myxomatous degeneration valves and disorganized distribution in rheumatic heart disease valves that correlated with clinical manifestations such as valve regurgitation or stenosis. Confocal microscopy analysis revealed a diverse pattern of distribution of collagen VI and lumican into RHD and MXD valves. Altogether, these results demonstrated distinct patterns of altered valve expression and tissue distribution/ organization of structural/matrix proteins that play important pathophysiological roles in both valve diseases.
dc.description.indexMEDLINE
dc.description.sponsorshipCommittee for the improvement of post graduation students (CAPES)
dc.description.sponsorshipImmunology Investigation Institute (iii) from National Institute for Science and Technology (INCT) through FAPESP-Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2008/573879]
dc.description.sponsorshipCNPQ-ConselhoNacional de PesquisaCNPq [2008/57881-0]
dc.identifier.citationPLOS ONE, v.12, n.1, article ID e0170191, 12p, 2017
dc.identifier.doi10.1371/journal.pone.0170191
dc.identifier.issn1932-6203
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/18791
dc.language.isoeng
dc.publisherPUBLIC LIBRARY SCIENCE
dc.relation.ispartofPlos One
dc.rightsopenAccess
dc.rights.holderCopyright PUBLIC LIBRARY SCIENCE
dc.subject.othergroup-a streptococcus
dc.subject.othercollagen
dc.subject.otheridentification
dc.subject.otherfever
dc.subject.otherprotein
dc.subject.othervitronectin
dc.subject.othervimentin
dc.subject.othercells
dc.subject.wosMultidisciplinary Sciences
dc.titleRheumatic Heart Disease and Myxomatous Degeneration: Differences and Similarities of Valve Damage Resulting from Autoimmune Reactions and Matrix Disorganization
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.citation.scopus10
hcfmusp.contributor.author-fmusphcCARLO DE OLIVEIRA MARTINS
hcfmusp.contributor.author-fmusphcLEA MARIA MACRUZ FERREIRA DEMARCHI
hcfmusp.contributor.author-fmusphcFREDERICO MORAES FERREIRA
hcfmusp.contributor.author-fmusphcPABLO MARIA ALBERTO POMERANTZEFF
hcfmusp.contributor.author-fmusphcCARLOS MANUEL DE ALMEIDA BRANDAO
hcfmusp.contributor.author-fmusphcRONEY ORISMAR SAMPAIO
hcfmusp.contributor.author-fmusphcGUILHERME SOBREIRA SPINA
hcfmusp.contributor.author-fmusphcJORGE ELIAS KALIL FILHO
hcfmusp.contributor.author-fmusphcEDECIO CUNHA NETO
hcfmusp.contributor.author-fmusphcLUIZA GUILHERME GUGLIELMI
hcfmusp.description.articlenumbere0170191
hcfmusp.description.issue1
hcfmusp.description.volume12
hcfmusp.origemWOS
hcfmusp.origem.pubmed28121998
hcfmusp.origem.scopus2-s2.0-85010993603
hcfmusp.origem.wosWOS:000396167300053
hcfmusp.publisher.citySAN FRANCISCO
hcfmusp.publisher.countryUSA
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