elastin and Rheumatic-Heart-Disease

Unlike myxomatous degeneration in Marfan syndrome, which has been reported to result from a mutation in the gene that codes for the extracellular structural protein fibrillin, no specific molecular abnormality has been documented to be the underlying cause of myxomatous degeneration in mitral valve prolapse syndrome (MVPS). The present study examined the distribution of fibrillin and other extracellular matrix proteins in patients with isolated MVPS.. Mitral valve leaflets from 7 MVPS patients and 5 rheumatic heart disease (RHD) patients were characterized immunohistochemically for fibrillin, elastin, collagen I, and collagen III distribution, and compared with five normal mitral valves.. In normal mitral valve leaflets immunostaining for fibrillin, elastin, collagen I, and collagen III revealed a fibrillary and laminar pattern in the atrialis and the spongiosa. In addition, both the collagens were present in the ventricularis, and the coarse bundles in the fibrosa exhibited alternating bandlike collagen I immunoreactivity. The staining patterns of fibrillin, elastin, and collagens I and III revealed distinctly different distribution in MVPS relative to the normal and RHD leaflets. MVPS leaflets in areas of myxoid degeneration displayed a more diffuse, weaker, and nonlaminar pattern of staining for fibrillin. Similar, but less severe abnormality of elastin, collagen I, and collagen III was also observed. Unlike diffuse abnormality in MVPS, the disruption of extracellular proteins in RHD only occurred at the site of the inflammatory damage, but the overall architecture was preserved.. The results of the current study suggest a primary role for abnormal fibrillin and other matrix proteins in producing myxoid degeneration of mitral valve leaflets in MVPS.

Topics: Adult; Aged; Collagen Type I; Collagen Type III; Elastin; Extracellular Matrix; Extracellular Matrix Proteins; Female; Fibrillins; Humans; Immunoenzyme Techniques; Male; Microfilament Proteins; Middle Aged; Mitral Valve; Mitral Valve Prolapse; Reference Values; Rheumatic Heart Disease

The connective matrix of 17 surgically excised mitral complexes from patients with clinical diagnosis of rheumatic carditis was evaluated by semi-quantitative histopathological, immunohistochemical and ultrastructural parameters. Different and concomitant patterns of loose and dense fibrosis were observed with variable constitution and organization of collagen I, III, IV, procollagen III, laminin, fibronectin and elastin. Loose fibrosis exhibited codistribution of all matrix components, Initial phase of fibrosis was characterized by deposition of all matrix components organized in a network pattern. In dense fibrosis a parallel disposition of type I collagen bundles predominated. In the denser (hyalin) fibrosis, the collagen exhibited abnormalities in fiber diameters and in fiber conformation (hyperfibers) and there was reduction or disappearance of other matrix components. The presence of these different kinds of connective matrix and the ultrastructural alterations in collagen fibers are associated to different stages of fibrosis organization and probably reflect changes in collagen susceptibility to degradation. These morphologic patterns may be related to the evolution (stability or reversibility) of rheumatic sequelae.

Topics: Adolescent; Adult; Aged; Child; Collagen; Connective Tissue; Elastin; Female; Fibronectins; Humans; Immunohistochemistry; Laminin; Male; Microscopy, Electron; Middle Aged; Rheumatic Heart Disease

Human mitral valves (32 floppy and 17 rheumatic) obtained at surgery were analysed and compared with 35 normal (autopsy) valves. Total amounts of collagen, proteoglycan and elastin were increased approx. 3-fold in floppy and rheumatic valves. The water content of rheumatic cusps was lower than normal. The most significant changes in floppy valves were the 59% increase in mean value of the proteoglycan content, a large increase in the ease of extractability of proteoglycans from 26.7 to 57.2% of the total and a 62% increase in mean value of the elastin content in the anterior cusps. Normal human mitral valve cusps contained a mean proportion of 29.3 (and chordae 26.6) type III collagen (as % of total types III + I collagen), the values increasing significantly to 33.2 and 36.3% respectively in chronic rheumatic disease. The ratio observed in floppy valves depended on the extent of secondary surface fibrosis, which could be demonstrated histologically; in valve cusps with considerable secondary fibrosis, the percentage of type III increased significantly (to 34.4%), whereas it decreased significantly (to 25.2%) when fibrosis was negligible. It is concluded that the ratio of collagen types in floppy valves reflects the extent of secondary fibrosis rather than the pathogenesis of the disrupted collagen in the central core of the valve.

Topics: Amino Acids; Collagen; Elastin; Glycosaminoglycans; Hexuronic Acids; Humans; Hydroxyproline; Mitral Valve; Mitral Valve Insufficiency; Procollagen; Proteoglycans; Rheumatic Heart Disease