Figure 1. Key endothelial structures and proteins that maintain endothelial integrity and barrier function ensuring that the intravascular solutes do not leak into the extravascular compartment. Tight junction proteins and adhesion junction proteins seal the intercellular junction between endothelial cells. Both tight junction and adhesion junction proteins bind to membrane proteins to form junctional complex and interact with actin cytoskeleton to increase the strength of cell-cell adhesion. Focal adhesions of endothelial cells with the underlying matrix provide an important structural basis for normal endothelial function and barrier properties. Caveolae, as vesicle carriers responsible for transcellular transport of albumin and other plasma proteins across endothelium, may help to maintain the transcapillary protein oncotic pressure gradient, which is critical for normal fluid balance homeostasis. The glycocalyx is a negatively charged surface coat of proteoglycans and absorbed plasma proteins lining the luminal surface of vascular endothelium. The net negative charge of the glycocalyx repels red blood cells and protects the vascular endothelium from platelet and leukocyte adhesion.
Figure 2. Proposed mechanisms of stressors in the maternal circulation that disturb endothelial barrier function and increase endothelial permeability in preeclampsia. Proposed stressors (toxic agents) in the maternal circulation may derive from placental trophoblasts (syncytiotrophoblast microvillus membrane particles (STMPs)), and activated leukocytes and platelets, which include oxidants (reactive oxygen species), proteases (thrombin, chymotrypsin, and MMPs), cytokines, angiogenic factor VEGF and its antagonist sFlt-1, etc. These stressors are able to affect on endothelial cells in multiple ways by disorganization of junctional proteins (tight junction - TJ; adhesion junction - AJ), rearrangement of cytoskeleton fibers, dephosphorylation of focal adhesion kinase (FAK), impairment of cell surface negative charge glycocalyx, depletion of cell energy ATP and downregulation of eNOS.