The Effects of Cell Contraction and Loss of Adhesion on the Apoptosis of Valve Interstitial Cells

Dystrophic calcification in sclerotic aortic valves is associated with apoptosis of myofibroblasts that differentiate from valve interstitial cells (VICs). The factors that regulate apoptosis in sclerotic valves are not known, but may include mechanical stimuli, as is the case in other fibrotic tissues. In support of this hypothesis, we have observed that VICs on stiff collagen matrices that simulate fibrotic tissue differentiate to myofibroblasts and form calcified aggregates that contain apoptotic cells [1]. However, the mechanisms by which cell aggregation leads to VIC apoptosis are unknown. In other cell types, cell contraction caused by release of matrix tension can induce cell apoptosis, but the mechanical transduction pathway regulating this process is unknown [2]. Similarly, cell rounding caused by disrupting the cytoskeletal network has been found to induce apoptosis [3], indicating the cytoskeletal network may play an important role in the cell shape-change related apoptosis pathways. Loss of adhesion between the cell and its matrix is also a well-documented cause for apoptosis of adherent cell types [4].