Valvular interstitical cells (VIC)
Valvular interstitial cells (VIC) represent a crucial and heterogeneous
cell population through the leaflet, distributed in all layers (23).
They are the most abundant cell type in the heart valves and resemble,
among others, fibroblasts and smooth muscle cells. VIC represent a
dynamic population responsible for the synthesis of extracellular matrix
and matrix degrading enzymes. Thus, they regulate and remodel collagen
and other essential components to assure the continuous valve repair
(23). The activation of VICs (including the production and secretion of
matrix) is regulated by mechanical stretch, local cellular signaling
(e.g. interaction with other types of cells from heart valves such as
valvular endothelial cells), microstructural factors, and hemodynamic
environments (24). It has also been theorized that VIC contraction, in
response to environment stimuli, may facilitate cell-to-cell
communication and act as a role in maintaining leaflet homeostasis (25).
The ability to answer to the surrounding environment makes VIC highly
plastic, with at least 5 distinct phenotypes described, from a quiescent
to an activated form (the 5 distinct VIC phenotypes include embryonic
progenitor endothelial/ mechenchymal cells, quiescent VIC, activated
VIC, postdevelopmental/ adult progenitor VIC and osteoblastic VIC) (23).
Although it may be interesting to explore all phenotypes, the quiescent
and the activated forms are the most relevant in this context. VIC in
adult valves are quiescent, without activity, with fibroblasts
characteristics (26). The plasticity of VICs is important for
development but plays also an important role in pathologic processes
(19). VIC plasticity is regulated by multiple factors, such as
environmental factors and host factor as age.
In the disease states, VIC progress from the quiescent fibroblast-like
phenotype to a contractile form, with enhanced production and secretion
of extracellular matrix, cytokines, proteases and growth factors (9,
10). VIC progression has direct consequences on the heart valve
function, as it has been shown that VIC contraction have measurable
effects on leaflet stiffness (28). When the activation persists and is
prolonged, VIC can differentiate into osteoblast-like cells (the
osteoblatic VIC phenotype), leading to calcific nodule formation and
valve calcifications (29). However, activation of VIC is not a
definitive process, as it can be reversiblly modulated (29).