Bilateral semilunar valve disease in a child with partial deletion of the Williams-Beuren syndrome region is associated with elastin haploinsufficiency

Division of Cardiology, Cincinnati Children's Hospital, Cincinnati, Ohio 45229-3039, USA.
The Journal of heart valve disease (Impact Factor: 0.75). 06/2006; 15(3):352-5.
Source: PubMed


Elastin is an extracellular matrix protein that is the primary component of elastic fibers, and is expressed in the great vessels as well as the semilunar and atrioventricular valves. Elastin haploinsufficiency, resulting from mutation or deletion of the elastin gene, is an important clinical problem that is typically characterized by arteriopathy. Herein is described a patient with elastin haploinsufficiency due to partial deletion of the Williams-Beuren syndrome region, resulting in bilateral semilunar valve disease and arteriopathy. Histochemical analysis of the aortic valve revealed decreased and disorganized elastin with loss of the normal trilaminar cusp organization. These findings suggest that elastin has a role in the pathogenesis of semilunar valve disease.

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Available from: Colleen A Morris, Sep 04, 2014
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    • "Heart valves facilitate unidirectional blood flow during the cardiac cycle and this is largely achieved by highly organized layers of connective tissue that each offer distinct biomechanical properties to facilitate opening and closing of the valve leaflets or cusps [1], [2]. In healthy valves, connective tissue homeostasis is mediated by valve interstitial cells (VICs), which in turn are regulated by a monolayer of valve endothelial cells (VECs) that overly the valve surface. "
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    PLoS ONE 07/2014; 9(7):e101425. DOI:10.1371/journal.pone.0101425 · 3.23 Impact Factor
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    • "he interstitial cells . Disruptions in the developmental pro - cesses that lead to normal valve histomorphology and the dysfunction of the two major valve cell types have been shown to be responsible for a series of valve pathological conditions ( Rabkin et al . 2002 ; Leask et al . 2003 ; Armstrong & Bischoff 2004 ; Rabkin - Aikawa et al . 2004 ; Hinton et al . 2006 ) . As melanocyte precursors reach the heart during the early stages of valve development and per - sist into adulthood ( Brito & Kos 2008 ) , it is reasonable to expect that their dysfunction might lead to valve abnorm - alities . Deficits associated with the proper specification , differentiation and migration of neural crest cells an"
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    Journal of The Royal Society Interface 08/2009; 6(40):1097-102. DOI:10.1098/rsif.2009.0174 · 3.92 Impact Factor
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    ABSTRACT: Heart valve disease is an important cause of morbidity and mortality worldwide. Little is known about valve disease pathogenesis, but increasing evidence implicates a genetic basis for valve disease, suggesting a developmental origin. Although the cellular and molecular processes involved in early valvulogenesis have been well described, less is known about the regulation of valve extracellular matrix (ECM) organization and valvular interstitial cell (VIC) distribution that characterize the mature valve structure. Histochemistry, immunohistochemistry, and electron microscopy were used to examine ECM organization, VIC distribution, and cell proliferation during late valvulogenesis in chicken and mouse. In mature valves, ECM organization is conserved across species, and developmental studies demonstrate that ECM stratification begins during late embryonic cusp remodeling and continues into postnatal life. Cell proliferation decreases concomitant with ECM stratification and VIC compartmentalization. Explanted, stenotic bicuspid aortic valves (BAVs) from pediatric patients were also examined. The diseased valves exhibited disruption of the highly organized ECM and VIC distribution seen in normal valves. Cusps from diseased valves were thickened with increased and disorganized collagens and proteoglycans, decreased and fragmented elastic fibers, and cellular disarray without calcification or cell proliferation. Taken together, these studies show that normal valve development is characterized by spatiotemporal coordination of ECM organization and VIC compartmentalization and that these developmental processes are disrupted in pediatric patients with diseased BAVs.
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