FIG. 3.

Major mechanosensors in valvular endothelial cells. Integrins bind to extracellular matrix to sense the dynamic mechanical environment surrounding the endothelial cell. Ions and antibodies are trapped by the glycocalyx in the surface of the cell, which translates to various downstream signal transduction pathways. Cell adhesion molecules (CAMs), such as cadherins or PECAM-1, sense changes in the mechanical environment between cells due to shear stress or other mechanical stimuli. These mechanosensors transduce the changes sensed through diverse signaling cascades (represented by black arrows) and through the actin cytoskeleton, which ultimately leads to transcriptional changes. The function of G protein-coupled receptors is not fully known in the valve, but their role in vascular endothelium suggests that they play a role in sensing the cellular mechanical environment and causing transcriptional changes in the nucleus. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars