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

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Autor(es):
Martins, Carlo de Oliveira ; Demarchi, Lea ; Ferreira, Frederico Moraes ; Alberto Pomerantzeff, Pablo Maria ; Brandao, Carlos ; Sampaio, Roney Orismar ; Spina, Guilherme Sobreira ; Kalil, Jorge ; Cunha-Neto, Edecio ; Guilherme, Luiza
Número total de Autores: 10
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 12, n. 1 JAN 25 2017.
Citações Web of Science: 1
Resumo

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. (AU)

Processo FAPESP: 08/57881-0 - Instituto de Investigação em Imunologia
Beneficiário:Jorge Elias Kalil Filho
Linha de fomento: Auxílio à Pesquisa - Temático