title: Rheumatic Heart Disease and Myxomatous Degeneration: Differences and Similarities of Valve Damage Resulting from Autoimmune Reactions and Matrix Disorganization.
abstract: Autoimmune 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.
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.|Institute of Investigation in Immunology, National Institute for Science and Technology, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Carlo de Oliveira
authors.initials: CO
authors.lastname: Martins
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Lea
authors.initials: L
authors.lastname: Demarchi
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.|Institute of Investigation in Immunology, National Institute for Science and Technology, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Frederico Moraes
authors.initials: FM
authors.lastname: Ferreira
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Pablo Maria Alberto
authors.initials: PM
authors.lastname: Pomerantzeff
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Brandao
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Roney Orismar
authors.initials: RO
authors.lastname: Sampaio
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Guilherme Sobreira
authors.initials: GS
authors.lastname: Spina
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.|Institute of Investigation in Immunology, National Institute for Science and Technology, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.|Institute of Investigation in Immunology, National Institute for Science and Technology, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
authors.affiliation: Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.|Institute of Investigation in Immunology, National Institute for Science and Technology, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Luiza
authors.identifier: http://orcid.org/0000-0003-0997-1498
authors.initials: L
authors.lastname: Guilherme
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D024142:Collagen Type VI / Q000032:analysis; D005109:Extracellular Matrix / Q000737:chemistry; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D000071234:Lumican / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000737:chemistry; D008945:Mitral Valve Prolapse / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000072417:Protein Domains; D040901:Proteomics; D012214:Rheumatic Heart Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D014746:Vimentin / Q000032:analysis; D019096:Vitronectin / Q000032:analysis
chemical_list: D024142:Collagen Type VI; C000604306:LUM protein, human; D000071234:Lumican; D014746:Vimentin; D019096:Vitronectin