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.