Figure 3.
The normal adult heart valve is well adapted to its physiological environment, able to withstand the unique hemodynamic/mechanical stresses under normal conditions. Under conditions of pathological injury or abnormal hemodynamic/mechanical stresses, VICs become activated through activation of VECs and by inflammation and associated cytokine and chemokine signals. Macrophages will also be activated. aVICs increase matrix synthesis, up-regulate expression of matrix-remodeling enzymes, migrate, proliferate and undergo apoptosis, and undergo osteoblast transformation. These processes are regulated by a variety of factors, several secreted by the aVIC. If the aVICs continue to promote these cellular processes, angiogenesis, chronic inflammation, fibrosis, and calcification result, leading to progressive clinical valve disease.