Heart valves
Natural heart valves are unique structures, adapted to allow unidirectional and nonobstructive blood flow. They are biologically dynamic structures, naturally designed to avoid regurgitation, thromboembolism, trauma to their molecular and cellular structures, or disruptive stress. To understand the pathophysiology of biological prosthetic valve’s dysfunction, it is crucial to understand the structure, biology and function of native heart valves.
In the embryonic developing heart valve, epithelial-to-mesenchymal transition occurs when cells from the endocardium differentiate into mesenchymal cells and migrate into the cardiac jelly that forms the pre-valve cardiac cushions (15). These cushions are rich in glycosaminonoglycans (GAG), such as hyaluronic acid, and signaling molecules responsible for further development of heart valves (1, 2). The cardiac cushions are responsible for the complex regulation of extracellular matrix proteins, producing an intricate and functional structure (16). Although the immature heart valve produces its own extracellular matrix in utero , their development is only completed in the postnatal life (1, 3). Characterizing embryonic progenitors of heart valve cells and development processes is important to understand basic pathogenesis in valvular disease. Exploring cellular and molecular pathways in valvular disease will eventually allow designing more intelligent and physiological heart valve tissues.
Development of heart valves leads to a layered, structured and highly specialized complex structure of adapted cells and extracellular matrix (18). Their configuration will allow heart valves to assure its highly specified function, maintain their strength and durability despite the regular and repetitive stress and strain. Heart valves also need to have elements that assure permanent repair and remodeling. Although there are 4 different heart valves with different configurations and functions, all of them have a similar layered patter of cells.
Valve leaflets are mainly constituted by collagen type I and III, proteoglycans, GAG and elastin (19). The leaflet has three layers, each with an important microstructure (Figure 1): 1) fibrosa : the outflow surface, with circumferentially and densely aligned packed collagen fibers, to enable a load-bearing function during diastole (20); 2) spongiosa : the middle layer rich in GAG, acts as a lubricant between the two other layers (20–22); and 3) ventricularis : the inflow surface, predominantly with elastin to provide elastic proprieties (20, 21). The arrangement and configuration of the extracellular matrix is responsible for the changes in shape and dimensions throughout the cardiac cycle.
Two major types of cells are present in the leaflets: the valvular endothelial cells and the interstitial valvular cells. Both groups of cells synergize to maintain the normal function of the valves.