Clinical and Pathological Features of Degenerative Mitral Valve Disease: Billowing Mitral Leaflet Versus Fibroelastic Deficiency

Matsumaru, Ichiro; Eishi, Kiyoyuki; Hashizume, Koji; Kawano, Hiroaki; Tsuneto, Akira; Hayashi, Tomayoshi

doi:10.5761/atcs.oa.13-00168

Cited by 11 publications

(10 citation statements)

References 23 publications

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“…This study has demonstrated differential pathomorphological features between FED and BD, which for long time have been viewed as 2 different stages of DMVD, but more recently based on gross pathologic features and clinical presentations, begun to be characterized as 2 separate diseases. 8,6,11,[19][20][21] To date, however, clear definitions of those entities have not been standardized or validated, and, moreover, histopathologic features are not always conclusive. Futhermore, the surgical classification remains difficult or impossible in some patients.…”

Section: Discussionmentioning

confidence: 99%

“…[24][25][26] In Marfan disease, antagonism of TGF-β signaling may prevent the pathologic prolongation and thickening of mitral valves. 20 TGF-β family members can also be inhibited by blocking type-1 angiotensin II receptor, 27,28 a pathway that is also implicated in myxomatous MVP. 29 This type of gene defect leads to a unique increase in mitogen-activated protein kinase signaling, most notably ERK, and that selective antagonism of this pathway reverses this effect.…”

Section: Potential Implicationsmentioning

confidence: 99%

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Comparative Histopathological Analysis of Mitral Valves in Barlow Disease and Fibroelastic Deficiency

Hjortnaes

Keegan

Bruneval

et al. 2016

Seminars in Thoracic and Cardiovascular Surgery

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Whether Barlow disease (BD) and fibroelastic deficiency (FED), the main causes of mitral valve prolapse (MVP), should be considered 2 distinct diseases remains unknown. Mitral valves from patients who required surgery for severe mitral regurgitation due to degenerative nonsyndromic MVP were analyzed. Intraoperative diagnosis of BD or FED was based on leaflet redundancy and thickness, number of segments involved, and annular dimension. The removed medial scallop of the posterior leaflet and attached chordae were used for histopathological and immunohistological assessment. Histologically, compared to normal controls (n = 3), BD (n = 14), and FED (n = 9) leaflets demonstrated an altered architecture and increased thickness. Leaflet thickness was greater and chordae thickness lower in BD than FED (P < 0.0001). In BD, increased thickness was owing to spongiosa expansion (proteoglycan accumulation) and intimal thickening on fibrosa and atrialis; in FED, local thickening was predominant on the fibrosa side, with accumulation of proteoglycan-like material around the chordae. Collagen accumulation was observed in FED leaflets and chords and decreased in BD. Fragmented elastin fibers were present in BD and FED; elastin decreased in BD but increased in FED leaflets and around chordae. Activated myofibroblasts accumulate in both diseased leaflets and chords, but more abundantly in FED chordae (P < 0.0001), independently of age, suggesting a role of these cells in chordal rupture. There were more CD34-positive cells in BD leaflets and in FED chordae (P < 0.01). In BD leaflets (but not chordae) proliferative Ki67-positive cells were more abundant (P < 0.01) and matrix metalloproteinase 2 levels were increased (P < 0.01) indicating tissue remodeling. Upregulation of transforming growth factor beta and pERK signaling pathways was evident in both diseases but more prominent in FED leaflets (continued on next page)(P < 0.001), with pERK upregulation in FED chordae (P < 0.0001). Most cellular and signaling markers were negligible in control valves. Quantitative immunohistopathological analyses demonstrated distinct changes between BD and FED valves: predominant matrix degradation in BD and increased profibrotic signaling pathways in FED, indicating that BD and FED are 2 different entities. These results may pave the way for genetic studies of MVP and development of preventive drug therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Potential Implicationsmentioning

confidence: 99%

Comparative Histopathological Analysis of Mitral Valves in Barlow Disease and Fibroelastic Deficiency

Hjortnaes

Keegan

Bruneval

et al. 2016

Seminars in Thoracic and Cardiovascular Surgery

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“…With the accumulation of mucopolysaccharides, collagen bundles become fragmented, coiled, and disrupted. As a result, the mitral valve becomes less stiff and more extensive [31][32][33].…”

Section: Pathologic Findingsmentioning

confidence: 98%

“…While BD houses an accumulation of mucopolysaccharide in the spongiosa layer, FED preserves the thickness of the auricularis, spongiosa, fibrosa, and ventricularis layers [31].…”

Section: Fibroelastic Deficiency Versus Barlow's Diseasementioning

confidence: 99%

Current Discoveries and Interventions for Barlow’s Disease

Siordia

2016

Curr Cardiol Rep

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“…For these reasons clinical phenotype has to be carefully considered when evaluating for gene expression in human mitral valve disease. FED contrasts with Barlow’s disease in that it has relatively fast onset (months) and is the result of deficiency in key connective tissue components including collagens, proteoglycans and elastin with chordae rupture being a common occurrence, for this reason Barlow’s disease is more analogous with canine MMVD [ 2 , 31 , 32 ]. Greenhouse and others [ 2 ] report the transcriptome for human MVP, but define that as FED.…”

Section: Comparative Pathologymentioning

confidence: 99%

Comparative Transcriptomic Profiling and Gene Expression for Myxomatous Mitral Valve Disease in the Dog and Human

Markby

Summers

MacRae

et al. 2017

Veterinary Sciences

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Myxomatous mitral valve disease is the single most important mitral valve disease in both dogs and humans. In the case of the dog it is ubiquitous, such that all aged dogs will have some evidence of the disease, and for humans it is known as Barlow’s disease and affects up to 3% of the population, with an expected increase in prevalence as the population ages. Disease in the two species show many similarities and while both have the classic myxomatous degeneration only in humans is there extensive fibrosis. This dual pathology of the human disease markedly affects the valve transcriptome and the difference between the dog and human is dominated by changes in genes associated with fibrosis. This review will briefly examine the comparative valve pathology and then, in more detail, the transcriptomic profiling and gene expression reported so far for both species.

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Clinical and Pathological Features of Degenerative Mitral Valve Disease: Billowing Mitral Leaflet Versus Fibroelastic Deficiency

Cited by 11 publications

References 23 publications

Comparative Histopathological Analysis of Mitral Valves in Barlow Disease and Fibroelastic Deficiency

Comparative Histopathological Analysis of Mitral Valves in Barlow Disease and Fibroelastic Deficiency

Current Discoveries and Interventions for Barlow’s Disease

Comparative Transcriptomic Profiling and Gene Expression for Myxomatous Mitral Valve Disease in the Dog and Human

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