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

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art_MARTINS_Rheumatic_Heart_Disease_and_Myxomatous_Degeneration_Differences_and_2017.PDF (1.7 MB)
Citações na Scopus
10
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article
Data de publicação
2017
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Scopus
Web of Science
PubMed
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PUBLIC LIBRARY SCIENCE
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Citação
PLOS ONE, v.12, n.1, article ID e0170191, 12p, 2017
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Unidades Organizacionais
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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.
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https://observatorio.fm.usp.br/handle/OPI/18791
Referências
  1. Banerjee T, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0090527
  2. Bella J, 2016, BIOCHEM J, V473, P1001, DOI 10.1042/BJ20151169
  3. Bober M, 2010, J INNATE IMMUN, V2, P160, DOI 10.1159/000232587
  4. Caira FC, 2006, J AM COLL CARDIOL, V47, P1707, DOI 10.1016/j.jacc.2006.02.040
  5. Carapetis JR, 2016, NAT REV DIS PRIMERS, V2, DOI 10.1038/nrdp.2015.84
  6. Chakravarti S, 1998, J CELL BIOL, V141, P1277, DOI 10.1083/jcb.141.5.1277
  7. Challa AA, 2011, MOL CELL BIOL, V31, P3773, DOI 10.1128/MCB.05263-11
  8. CUNNINGHAM MW, 1986, J EXP MED, V164, P998, DOI 10.1084/jem.164.4.998
  9. Dinkla K, 2003, J CLIN INVEST, V111, P1905, DOI 10.1172/JCI200317247
  10. Dinkla K, 2007, J BIOL CHEM, V282, P18686, DOI 10.1074/jbc.M701047200
  11. Fae KC, 2008, J AUTOIMMUN, V31, P136, DOI 10.1016/j.jaut.2008.04.023
  12. Gildner CD, 2014, MATRIX BIOL, V34, P33, DOI 10.1016/j.matbio.2014.01.017
  13. Guilherme L, 2011, ADV CLIN CHEM, V53, P31, DOI 10.1016/S0065-2423(11)53002-1
  14. He YH, 2011, J AM SOC ECHOCARDIOG, V24, P399, DOI 10.1016/j.echo.2011.01.001
  15. Jiang L, 2009, CLIN EXP IMMUNOL, V155, P216, DOI 10.1111/j.1365-2249.2008.03747.x
  16. Lukomski S, 2001, INFECT IMMUN, V69, P1729, DOI 10.1128/IAI.69.3.1729-1738.2001
  17. Lukomski S, 2000, INFECT IMMUN, V68, P6542, DOI 10.1128/IAI.68.12.6542-6553.2000
  18. Santos KS, 2014, CLIN MED INSIGHTS CA, V8, P79, DOI 10.4137/CMC.S17622
  19. Pellerin D, 2002, HEART, V88, P20
  20. Perkins DN, 1999, ELECTROPHORESIS, V20, P3551, DOI 10.1002/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2
  21. PREISSNER KT, 1991, ANNU REV CELL BIOL, V7, P275, DOI 10.1146/annurev.cb.07.110191.001423
  22. Remenyi B, 2016, LANCET, V387, P1335, DOI 10.1016/S0140-6736(16)00547-X
  23. Ricard-Blum S, 2011, CSH PERSPECT BIOL, V3, DOI 10.1101/cshperspect.a004978
  24. Steer AC, 2009, LANCET INFECT DIS, V9, P611, DOI 10.1016/S1473-3099(09)70178-1
  25. Tandon R, 2013, NAT REV CARDIOL, V10, P171, DOI 10.1038/nrcardio.2012.197

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/11
Artigos e Materiais de Revistas Científicas - LIM/19
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