PLoS One. 2017 Jan 25;12(1):e0170191. doi: 10.1371/journal.pone.0170191.

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

Carlo de Oliveira Martins 1,2, Lea Demarchi1, Frederico Moraes Ferreira1,2, Pablo Maria Alberto Pomerantzeff1, Carlos Brandao1, Roney Orismar Sampaio1, Guilherme S. Spina1, Jorge Kalil1, 2, Edecio Cunha-Neto 1, 2 & Luiza Guilherme1, 2

(1) Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil.

(2) Institute of Investigation in Immunology, National Institute for Science and Technology,  University of São Paulo, São Paulo, Brazil.

PubMed link

 

Supplement:

Rheumatic heart disease (RHD) and myxomatous degeneration (MXD) present diverse etiologies and mechanisms that culminate in valve damage.

RHD lesions are due to local inflammation and tissue injury with subsequent cellular matrix disorganization leading to valvular dysfunction. Valvular regurgitation and/or stenosis (supplementary Figure 1) lesions involve inflammatory mediators that attract leukocytes, monocytes, T- and B-lymphocytes.

MXD differently is due to elastic fiber alterations that lead to valve prolapse and chordae rupture and mucopolysaccharide accumulation that causes collagen disorganization and elastic fiber fragmentation.

Both diseases presented a set of valve proteins with differential and/or altered expression. In the present work described distinct patterns of altered valve expression of vimentin, collagen, lumican and vitronectin due to protein cleavage or degradation in both RHD and MXD valves.

Briefly, our results showed in RHD valves a disorganized patter of vimentin, reduced expression of collagen VI, an essential structural component of connective tissue, responsible for tissue integrity, repair and growth and serves as target for adhesion by S. pyogenes, through collagen-binding proteins. In addition, these proteins are target of RF/RHD autoimmune reactions by both T and B lymphocytes. On the other hand, collagen VI was diffusely expressed in MXD valves and diffuses lumican distribution was also observed.

The results presented in this article suggested that the altered expression of these proteins in both RHD and DMX valvular tissue may play important pathophysiological role.

 

 

 

Additional macroscopic RHD valve lesions

Figure: Post-rheumatic mitral regurgitation and stenosis, surgical excision (below): Atrial (a) and ventricular (v) aspects of anterior mitral cusp showing diffuse fibrosis and leaflet distortion with marked retraction at the closure line (*), commissural adherence (arrow), and a prominent fibrous ridge at the free edge (dotted line). There is marked thickening, fusion and retraction of the chords (arrowheads) and fibrosis in the papillary muscle tips (pm). Kindly provided by Dr Lea DeMarchi from Pathological Anatomy Lab, Heart Institute (InCor), Clinical Hospital, School of Medicine, University of São Paulo.