Maruyama I
Department of Clinical, Laboratory and Molecular Medicine, Kagoshima University School of Medicine, Kagoshima City, Japan.
Lupus. 1998;7 Suppl 2:S41-3. doi: 10.1177/096120339800700210.
Endothelial cells form a multifunctional cell lining that covers all of the inner surface of blood vessels and regulates several important physiological and pathological reactions. These include inflammation/immune reaction, blood vessel tonus, hemostasis/thrombosis, angiogenesis and so on. Thus, abnormalities of endothelial function may play crucial roles in the development of angitis syndrome, thrombosis/embolism, bleeding disseminated intravascular coagulation (DIC), and neovascularization in some pathological states including tumor growth and diabetic retinopathy. Research on endothelial cells now forms a new frontier termed 'Endotheliology'. Recent advances of the functional and structural aspects of endothelial cells are reviewed here mainly from the viewpoint of endothelial regulation of coagulation and the fibrinolytic system. First we show that the natural endothelial membrane protein thrombomodulin is localized not only on apical endothelial surface but also in caveolae. Since it has been reported that such factors involved in coagulation/fibrinolysis as tissue factor, tissue factor pathway inhibitor (TFPI), thrombin receptor and urokinase receptor are also localized in the caveolae, this membrane structure may act as a special component to regulate coagulation/fibrinolysis on the endothelial membrane surface. Next we demonstrate the signaling pathway of the thrombin receptor. Thrombin cleaves the N-terminus of the receptor as a substrate, 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 receptor activates NF-kappaB 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 platelets from diabetes patients.
内皮细胞形成一种多功能细胞内衬，覆盖血管的所有内表面，并调节多种重要的生理和病理反应。这些反应包括炎症/免疫反应、血管张力、止血/血栓形成、血管生成等。因此，内皮功能异常可能在血管炎综合征、血栓形成/栓塞、出血性弥散性血管内凝血（DIC）以及包括肿瘤生长和糖尿病视网膜病变在内的某些病理状态下的新生血管形成中起关键作用。目前对内皮细胞的研究形成了一个新的领域，称为“内皮学”。本文主要从内皮细胞对凝血和纤溶系统的调节角度，综述内皮细胞功能和结构方面的最新进展。首先，我们发现天然内皮膜蛋白血栓调节蛋白不仅定位于内皮细胞顶端表面，还存在于小窝中。由于有报道称参与凝血/纤溶的组织因子、组织因子途径抑制剂（TFPI）、凝血酶受体和尿激酶受体等因子也定位于小窝中，这种膜结构可能作为一种特殊成分在内皮膜表面调节凝血/纤溶。接下来，我们展示了凝血酶受体的信号通路。凝血酶将受体的N端作为底物切割，暴露出一个新的N端。这个新暴露的N端作为配体激活血小板、内皮细胞和血管平滑肌细胞。我们已经确定，来自凝血酶受体的信号通过激活蛋白C激酶、酪氨酸激酶和丝裂原活化蛋白激酶（MAP激酶）激活核因子κB，并导致细胞增殖。我们还表明，该受体在糖尿病患者的血小板上过度表达。
