Is aortic wall degeneration related to bicuspid aortic valve anatomy in patients with valvular disease?

Russo, Claudio; Cannata, Aldo; Lanfranconi, Marco; Vitali, Ettore; Garatti, Andrea; Bonacina, Edgardo

doi:10.1016/j.jtcvs.2007.11.072

Cited by 112 publications

(103 citation statements)

References 18 publications

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“…In humans, most BAVs result from fusion of either the right-coronary and left-coronary leaflets (R-L) or the right-coronary and noncoronary leaflet (R-N). R-N BAV is associated with a greater degree of valve dysfunction, and it has also become clear over the years that BAV morphology is of prognostic relevance in the management of patients with BAVs (43)(44)(45). Work in animal models suggests that the 2 subtypes may be distinct etiological entities; R-N BAVs would result from defective development of the cardiac OFT endocardial cushions, whereas R-L BAVs result from an extra fusion of the septal and parietal ridges (38).…”

Section: Discussionmentioning

confidence: 99%

Loss of Gata5 in mice leads to bicuspid aortic valve

Laforest¹,

Andelfinger²,

Nemer³

2011

J. Clin. Invest.

163

146

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Bicuspid aortic valve (BAV), the leading congenital heart disease, occurs in 1%-2% of the population. Genetic studies suggest that BAV is an autosomal-dominant disease with reduced penetrance. However, only 1 gene, NOTCH1, has been linked to cases of BAV. Here, we show that targeted deletion of Gata5 in mice leads to hypoplastic hearts and partially penetrant BAV formation. Endocardial cell-specific inactivation of Gata5 led to BAV, similar to that observed in Gata5 -/-mice. In all cases, the observed BAVs resulted from fusion of the right-coronary and noncoronary leaflets, the subtype associated with the more severe valve dysfunction in humans. Neither endocardial cell proliferation nor cushion formation was altered in the absence of Gata5. Rather, defective endocardial cell differentiation, resulting from the deregulation of several components of the Notch pathway and other important endocardial cell regulators, may be the underlying mechanism of disease. The results unravel a critical cell-autonomous role for endocardial Gata5 in aortic valve formation and identify GATA5 as a potential gene responsible for congenital heart disease in humans. Mice with mutated Gata5 alleles represent unique models to dissect the mechanisms underlying degenerative aortic valve disease and to develop much-needed preventive and therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Loss of Gata5 in mice leads to bicuspid aortic valve

Laforest¹,

Andelfinger²,

Nemer³

2011

J. Clin. Invest.

163

146

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show abstract

“…Moreover, BAV patients with fusion of the left coronary and right coronary cusps were significantly younger at the time of surgery and had a significantly larger aortic root diameter versus BAV patients with fusion of the right coronary and non-coronary cusps. The investigators of this study concluded that the presence of more severe histopathological changes at a younger age, and a significantly larger aortic root diameter in BAV patients with fusion of the left coronary and right coronary cusps, may be predictive of a more accelerated and "malignant" BAV phenotype (Russo et al, 2007).…”

Section: Different Cusps Fusion Patterns In Bav Diseasementioning

confidence: 80%

“…There is emerging evidence from the recent literature that the different cusp fusion patterns in BAV disease are associated with specific lesions of the proximal aorta. The histopathological grading of the of aortic wall changes in patients who underwent surgery for BAV disease demonstrated a more severe degree of wall degeneration in the ascending aorta in patients with fusion of the left coronary and right coronary cusps versus fusion of the right coronary and non-coronary cusps (Russo et al, 2007). The prevalence of fibrosis, cystic medial necrosis, elastic fragmentation, and inflammation has been shown to be significantly higher in patients with fusion of the left coronary and right coronary cusps.…”

Section: Different Cusps Fusion Patterns In Bav Diseasementioning

confidence: 97%

Novel Phenotypes in Bicuspid Aortic Valve Disease

Girdauskas¹,

Borger²,

Kuntze³

2011

Aortic Valve

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“…There is a release of matrix metalloproteinases (MMPs), injury to the ECM including elastin fragmentation, cell death and in consequence the loss of support and flexibility of the aortic wall. These changes in the middle layer of the aortic wall lead to the development and expansion of the aortic aneurysm [1,4,11]. The incidence of TAAD in patients with BAV is estimated at about 30-40%, so it is three times higher than in patients with tricuspid valve, in which it is about 12% [1,3].…”

Section: Discussionmentioning

confidence: 99%