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. 2017 May;32(3):239-245.
doi: 10.1097/HCO.0000000000000384.

Genetic basis of aortic valvular disease

Affiliations

Genetic basis of aortic valvular disease

Sara N Koenig et al. Curr Opin Cardiol. 2017 May.

Abstract

Purpose of review: Aortic valve disease is relatively common and encompasses both congenital and acquired forms. Bicuspid aortic valve (BAV) is the most common type of cardiac malformation and predisposes to the development of calcific aortic valve disease (CAVD). Since the description of the link between NOTCH1, BAV and CAVD approximately a decade ago, there have been significant advances in the genetic and molecular understanding of these diseases.

Recent findings: Recent work has defined the congenital cardiac phenotypes linked to mutations in NOTCH1, and in addition, novel etiologic genes for BAV have been discovered using new genetic technologies in humans. Furthermore, several mouse models of BAV have been described defining the role of endothelial Notch1 in aortic valve morphogenesis, whereas others have implicated new genes. These murine models along with other cell-based studies have led to molecular insights in the pathogenesis of CAVD.

Summary: These findings provide important insights into the molecular and genetic basis of aortic valve malformations, including BAV, specifically highlighting the etiologic role of endothelial cells. In addition, numerous investigations in to the mechanisms of CAVD demonstrate the importance of developmental origins and signaling pathways as well as communication between valve endothelial cells and the underlying interstitial cells in valve disease onset and progression.

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Conflict of interest statement

The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1. Overview of aortic valve structure
The aortic valve is a highly organized structure composed of cellular and extracellular components. Each valve cusp is surrounded by a continuous, single layer of valve endothelial cells and interspersed by valve interstitial cells. The extracellular matrix is highly organized and largely composed of elastin fibers in the atrialis/ventricularis (dark grey), proteoglycans in the spongiosa (blue) and collagens (yellow) in the fibrosa and these are arranged according to blood flow (red arrows).
Figure 2
Figure 2. Congenital bicuspid aortic valve with the development of calcification
(A, B) The normal aortic valve consists of three cusps, and during diastole (A) and systole (B) the cusps sufficiently coapt and fully open respectively to regulate unidirectional blood flow. In contrast, bicuspid aortic valves consist of two cusps that results in narrowing (D) and leads to lifelong changes in valve biomechanics, stenosis and increases the risk of calcification (shown as nodules in C, D).

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