Anatomy and Histology
The normal aortic valve maintains unidirectional blood flow from the left ventricle into the aorta. It is a supple membrane that opens and closes with each heartbeat more 
than 100,000 times a day. The healthy aortic valve comprises three leaflets and is located at the junction between the left ventricular outflow tract and the aortic root. The internal collagen framework of the leaflets is arranged in three distinct layers, which – from the aortic to ventricular surface – are the fibrosa, spongiosa, and ventricularis (see Figure 1 ). This leaflet structure is covered on both the ventricular and aortic surfaces by endothelium in continuity with both the ventricular endocardium and the aortic endothelium. Each layer of the aortic valve has a distinct structure and function. The fibrosa, with its dense connective tissue, contains circumferentially oriented collagen fibres that provide most of the strength of the leaflets. The spongiosa is found at the bases of the leaflets. It contains a loose matrix of mucopolysaccharides, and provides a cushion to resist compressive forces and facilitate movements between the fibrosa and ventricularis during leaflet motion. The ventricularis layer contains radially oriented elastin and contributes to flexibility, allowing for changes in leaflet shape during opening and closing. Under normal conditions, all three layers are avascular with no cellular infiltrates and are innervated by adrenergic and cholinergic neural networks.5–7 To remain pliable, the aortic valve must undergo continuous repair throughout life. Accumulation of fibrotic tissue and calcium in a valve leads to decreased pliability and narrowing of the valve orifice.8,9
Valve interstitial cells (VICs) are found in each of these layers, and have distinct sub-populations that regulate homeostasis within the valve leaflets.10–12 In addition to the common tricuspid anatomy of the aortic valve, a congenital bicuspid valve is found in 0.5–1.4 % of the general population, giving rise to differential biomechanical forces – both on the valve and the aortic wall.13–15