Endothelial Cells: Source, Barrier, and Target of Defensive Mediators

Endothelium is strategically located at the interface between blood and interstitial tissues, placing thus endothelial cell as a key player in vascular homeostasis. Endothelial cells are in a dynamic equilibrium with their environment and constitute concomitantly a source, a barrier, and a target of defensive mediators. This review will discuss the recent advances in our understanding of the complex crosstalk between the endothelium, the complement system and the hemostasis in health and in disease. The first part will provide a general introduction on endothelial cells heterogeneity and on the physiologic role of the complement and hemostatic systems. The second part will analyze the interplay between complement, hemostasis and endothelial cells in physiological conditions and their alterations in diseases. Particular focus will be made on the prototypes of thrombotic microangiopathic disorders, resulting from complement or hemostasis dysregulation-mediated endothelial damage: atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Novel aspects of the pathophysiology of the thrombotic microangiopathies will be discussed.