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

Date Published: January 25, 2017

Publisher: Public Library of Science

Author(s): Carlo de Oliveira Martins, Lea Demarchi, Frederico Moraes Ferreira, Pablo Maria Alberto Pomerantzeff, Carlos Brandao, Roney Orismar Sampaio, Guilherme Sobreira Spina, Jorge Kalil, Edecio Cunha-Neto, Luiza Guilherme, Katherine Yutzey.


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.

Partial Text

Rheumatic fever (RF) results after approximately two weeks of a throat infection by Streptococcus pyogenes and affects non-treated susceptible children and teenagers. Rheumatic heart disease (RHD) is the major sequel occurring in approximately 60% of the cases. Recently, an update of the disease noted that greater than 34 million cases of RHD are estimated to occur worldwide, causing over 10 million disability adjusted life years and 275,000 deaths each year (reviewed by Carapetis et al. and by Remenyi et al.) [1,2].

As RHD and MXD present diverse etiologies and mechanisms that culminate in valve damage, in the present work our aim was to evaluated the pattern of distribution of some proteins in the valve tissue of both diseases. Interestingly, we observed that collagen VI protein presented similar pattern in the valve tissue of both diseases, while other proteins here analyzed displayed distinct pattern.




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