BIOLOGY OF ENDOTHELIUM

Endothelial cells form a multifunctional cell lining that covers all o f the inner surface of blood vessels and regulates several important p hysiological and pathological reactions. These include inflammation/im mune reaction, blood vessel tonus, hemostasis/thrombosis, angiogenesis and so on. Thus, abnormalities of endothelial function may play cruci al roles in the development of angitis syndrome, thrombosis/embolism: bleeding disseminated intravascular coagulation (DIC), and neovascular ization in some pathological slates including tumor growth and diabeti c retinopathy. Research on endothelial cells now forms a new frontier termed 'Endotheliology'. Recent advances of the functional and structu ral aspects of endothelial cells are reviewed here mainly from the vie wpoint of endothelial regulation of coagulation and the fibrinolytic s ystem. First we show that the natural endothelial membrane protein thr ombomodulin is localized not only on apical endothelial surface but al so in caveolae. Since it has been reported that such factors involved in coagulation/fibrinolysis as tissue factor, tissue factor pathway in hibitor (TFPI), thrombin receptor and urokinase receptor are also loca lized in the caveolae, this membrane structure may act as a special co mponent to regulate coagulation/fibrinolysis on the endothelial membra ne surface. Next we demonstrate the signaling pathway of the thrombin receptor. Thrombin cleaves the N-terminus of the receptor as a substra te, exposing a new N-terminus. This newly exposed N-terminus acts as a ligand and activates platelets, endothelial cells and vascular smooth -muscle cells. We have identified that the signal from the thrombin re ceptor activates NF-kappa B through the activation of protein C kinase , tyrosine kinase and MAP kinase, and results in proliferation of the cells. We have also shown that the receptor is over-expressed on plate lets from diabetes patients.