69 - Introductory Essay: Endothelial Cell Coupling

Summary

Endothelial cells (ECs), by virtue of their location at the interface between the bloodstream and the vessel wall, must integrate bidirectional signaling inputs and generate appropriate responses. These responses in turn can affect both EC interaction with the flowing blood and the circulating blood cells, as well as affect the function of the vessel wall. Thus, these deceptively simple looking cells are charged with a highly complex task of responding to and modifying the behavior of the liquid phase (plasma) and the solid phase (vessel wall) environments.

This integrative signaling function performed by the endothelium includes a number of components, including sensors of the physical environment such as the rate of blood flow (shear stress), of the circulating growth factors and cytokines, and of the circulating cells. In addition, the type of matrix the EC rests on, and cells it is in contact with, including other ECs, provide additional inputs into the complex integration matrix. As a practical example of this challenge, let us consider that, under certain circumstances, an EC may be called on to deal with a variety of inputs, including signals from multiple soluble ligands binding to tyrosine kinase receptors (e.g., vascular endothelial growth factor [VEGF], fibroblast growth factor [FGF], platelet-derived growth factor [PDGF]); serine/threonine kinases (e.g., epidermal growth factor [EGF]); G-protein-coupled receptors (e.g., thrombin); input from binding circulating cells via cellular adhesion molecules; signals from the extracellular matrix via integrins, syndecans, and other adhesion molecules; and signals from other adjoining ECs via tight junctions.