ISSN:1424-8832    

DOI:10.1159/000215805

出版商:S. Karger AG    

年代:1988

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000215806

出版商:S. Karger AG    

年代:1988

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000215807

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The endothelium plays an active role in the regulation of the coagulation mechanism. Multiple anticoagulant properties are operative on the cell surface in homeostasis. In the protein C/protein S pathway, for example, endothelium provides cofactors promoting activation of protein C, assembly of the activated protein C/protein S complex, and synthesizes protein S. In contrast, following exposure to cytokines and other pathologic stimuli, endothelial cell activation occurs. This activated state includes upregulation of procoagulant properties, such as tissue factor, with concomitant downregulation of anticoagulant cofactors, such as thrombomodulin. Modulation of endothelial cell coagulant properties by cytokines provides a mechanism linking activation of the clotting mechanism to the cellular response to environmental stimuli.

ISSN:1424-8832    

DOI:10.1159/000215808

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Molecular genetics, biochemistry, and cell biology of thromboplastin are briefly reviewed with special emphasis on its biosynthesis by endothelial cells.

ISSN:1424-8832    

DOI:10.1159/000215809

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Endothelium forms the inner lining of all blood vessels and, as a consequence, is in direct contact with the blood. Because of this and the synthesis and secretion of hemostatic components, the endothelium is able to modulate coagulation and fibrinolysis. An important hemostatic factor synthesized by endothelial cells is the von Willebrand factor (vWF). vWF is a large plasma glycoprotein which promotes the adhesion of platelets to the vessel wall after a vascular injury. vWF is initially synthesized as a pre-pro-polypeptide. During its transport to the outside of the cell, the single-chain polypeptides are assembled into multimers. The pro-polypeptide can be cleaved and also be secreted. Free pro-polypeptide is identified as von Willebrand antigen II, a plasma glycoprotein of unknown function. Plasma vWF consists of a heterogenous series of multimers, composed of an apparently single-type glycoprotein subunit, linked together by disulfide bonds. The hemostatic potency of vWF was shown to increase with increasing multimer size. Therefore, the multimeric assembly of vWF is a crucial aspect in vWF biosynthesis. Furthermore, vWF synthesized by endothelial cells can either be secreted constitutively or stored and released upon stimulation of the endothelial cell. In this review, data are presented which contribute to the understanding of the biosynthetic pathway and complex processing which vWF has to undergo before it is secreted by the endothelial cell. These data have allowed a prediction of the sequential events underlying vWF biosynthesis, processing, multimer assembly, and secretion.

ISSN:1424-8832    

DOI:10.1159/000215810

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Endothelial cells synthesize and store von Willebrand factor. We have studied the storage and secretion of von Willebrand factor in cultured human umbilical vein endothelial cells. In particular, we were interested in the nature of the storage compartment and the effects of perturbation on the storage and secretion processes. The storage compartment for von Willebrand factor was isolated from homogenates of endothelial cells. By an immunostaining technique the isolated vesicles stained for von Willebrand factor. The staining pattern was similar to that of Weibel-Palade bodies in intact endothelial cells. We concluded that the storage compartment containing von Willebrand factor is identical to the Weibel-Palade body. The von Willebrand factor of the isolated storage vesicles is predominantly constructed of polypeptide chains with a Mr of 220 kD. On the other hand, von Willebrand factor continuously secreted by endothelial cells is constructed of both a 220 kD and a larger precursor (apparent Mr of 275 kD) subunit. The storage vesicles contain von Willebrand factor that supports ristocetin-induced platelet aggregation. Thus, endothelial cells store fully processed, biologically active von Willeband factor within Weibel-Palade bodies. Short-term ( < 1 h) treatment of endothelial cells with the perturbing phorbol ester 4β-phorbol-12-myristate-13-acetate (PMA) results in release of cellular stored von Willebrand factor. 24–48 h after exposure to PMA the endothelial cell distribution of von Willeband factor is changed distinctly. While the contents of the von Willebrand factor storage sites in the cells are gradually restored within 48 h, enhanced amounts of von WiUebrand factor are secreted into the medium. The number as well as the size of von Willebrand factor storage granules in the endothelial cells increase after exposure to phorbol ester, as determined by immunofiuorescence microscopy. Phorbol ester treated cells release stored von Willebrand factor 48 h after they have been stimulated. PMA decreases the von Willebrand factor contents of the extracellular matrix; the deposition of von Willebrand factor in the subendothelium is blocked by PMA, whereas the degradation of matrix von Willebrand factor is not affected. Thus, perturbation of endothelial cells changes the cellular distribution of von Willebrand fact

ISSN:1424-8832    

DOI:10.1159/000215811

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Several observations indicate that endothelial cells interact with fibrinogen, fibrin, and their derivative products. The main biological function of fibrinogen on endothelial cells so far identified is its ability to promote adhesion, motility, and cytoskeletal organization of these cells. In other words, when fibrinogen is bound to a substratum, it behaves as a matrix protein like fibronectin, collagen, or vitronectin. Fibrinogen specifically binds to endothelial cells with low affinity and with a high number of binding sites. In addition, the putative fibrinogen receptor in endothelial cells appears to be related to the other extracellular matrix protein receptors.

ISSN:1424-8832    

DOI:10.1159/000215812

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

In this communication some of the important regulatory mechanisms involving endothelial cell surface associated anticoagulant reactions as well as endothelial cell surface expressed receptors which directly contribute to the inhibition of coagulation are reviewed. In particular, the mechanism of action of protease inhibitors such as antithrombin III, heparin cofactor II, or protease nexin I and their possible interaction with glycosaminoglycan components of the endothelial cells is critically summarized. Thrombin binding to endothelial cells, in particular to thrombomodulin, is believed to be a major event in the induction of anticoagulatory mechanisms such as the protein C/protein S system which warrant a balanced hemostatic system. Additional components such as vascular anticoagulant or extrinsic pathway inhibitor may also contribute to the anticoagulant potential of the vessel wall. Furthermore, the modulation of these membrane-associated anticoagulant reactions by other components such as heparin-binding proteins is discussed.

ISSN:1424-8832    

DOI:10.1159/000215813

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Plasminogen activators (PAs) play a role in fibrinolysis, tissue remodelling, tumor invasion, and reparative processes. Vascular endothelial cells produce tissue-type PA (t-PA), an important regulator of fibrinolysis, and PA inhibitor 1. They can also synthesize a second type of PA, urokinase-type PA (u-PA). The regulation of synthesis and secretion of these PAs by human and bovine endothelial cells in vitro is reviewed. The synthesis of t-PA and u-PA varies between endothelial cells, depending on their vascular origin. The production of PA activity by endothelial cells is regulated at various levels: (1) induction of newly synthesized t-PA or u-PA molecules; (2) rapid release of t-PA from endothelial cells; (3) conversion of single-chain u-PA in the more active two-chain u-PA; (4) interaction of PAs with cellular receptors and matrix components, and (5) interaction of PAs with specific inhibitors.

ISSN:1424-8832    

DOI:10.1159/000215814

出版商:S. Karger AG    

年代:1988

数据来源: Karger