Expression of the vascular endothelial cell protein C receptor in epithelial tumour cells

2002 ◽  
Vol 38 (11) ◽  
pp. 1535-1542 ◽  
Author(s):  
George L. Scheffer ◽  
Marcel J. Flens ◽  
Sandra Hageman ◽  
Miguel A. Izquierdo ◽  
Robert H. Shoemaker ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Protein C ◽  
Vascular Endothelial Cell ◽  
Tumour Cells ◽  
Cell Protein ◽  
Vascular Endothelial ◽  
Epithelial Tumour

scholarly journals Homocysteine, an atherogenic stimulus, reduces protein C activation by arterial and venous endothelial cells

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 895-901 ◽  
Author(s):  
GM Rodgers ◽  
MT Conn
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Protein C ◽  
Vascular Endothelial Cell ◽  
Activated Protein C ◽  
Cell Protein ◽  
Blood Levels ◽  
Factor V ◽  
Elevated Blood ◽  
Cultured Endothelial Cells

Abstract Elevated blood levels of homocysteine are associated with atherosclerosis and thrombotic disease. We previously reported that treatment of cultured endothelial cells with homocysteine increased endogenous factor V activity by activation of the cofactor. Because endothelial cell-associated factor Va would be regulated by the protein C mechanism, the ability of homocysteine-treated arterial and venous endothelial cells to activate protein C was investigated. Both arterial and venous endothelial cells activated protein C; 0.6 mmol/L homocysteine reduced endothelial cell protein C activation by 12%. Maximal inhibition (90%) of protein C activation occurred with 7.5 to 10 mmol/L homocysteine after 6 to 9 hours of incubation. Metabolism of homocysteine was not accelerated by cultured endothelial cells. Investigation of the mechanism(s) by which homocysteine reduced protein C activation indicated that the metabolite did not induce an inhibitor to activated protein C, but in low concentrations acted as a competitive inhibitor to thrombin. These data suggest that perturbation of the vascular endothelial cell protein C mechanism by homocysteine may contribute to the thrombotic tendency seen in patients with elevated blood levels of this metabolite.

Homocysteine, an atherogenic stimulus, reduces protein C activation by arterial and venous endothelial cells

Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 895-901 ◽  
Author(s):  
GM Rodgers ◽  
MT Conn
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Protein C ◽  
Vascular Endothelial Cell ◽  
Activated Protein C ◽  
Cell Protein ◽  
Blood Levels ◽  
Factor V ◽  
Elevated Blood ◽  
Cultured Endothelial Cells

Elevated blood levels of homocysteine are associated with atherosclerosis and thrombotic disease. We previously reported that treatment of cultured endothelial cells with homocysteine increased endogenous factor V activity by activation of the cofactor. Because endothelial cell-associated factor Va would be regulated by the protein C mechanism, the ability of homocysteine-treated arterial and venous endothelial cells to activate protein C was investigated. Both arterial and venous endothelial cells activated protein C; 0.6 mmol/L homocysteine reduced endothelial cell protein C activation by 12%. Maximal inhibition (90%) of protein C activation occurred with 7.5 to 10 mmol/L homocysteine after 6 to 9 hours of incubation. Metabolism of homocysteine was not accelerated by cultured endothelial cells. Investigation of the mechanism(s) by which homocysteine reduced protein C activation indicated that the metabolite did not induce an inhibitor to activated protein C, but in low concentrations acted as a competitive inhibitor to thrombin. These data suggest that perturbation of the vascular endothelial cell protein C mechanism by homocysteine may contribute to the thrombotic tendency seen in patients with elevated blood levels of this metabolite.

scholarly journals FVIIa (Factor VIIa) Induces Biased Cytoprotective Signaling in Mice Through the Cleavage of PAR (Protease-Activated Receptor)-1 at Canonical Arg41 (Arginine41) Site

2020 ◽  
Vol 40 (5) ◽  
pp. 1275-1288 ◽  
Author(s):  
Vijay Kondreddy ◽  
Usha R. Pendurthi ◽  
Xiao Xu ◽  
John H. Griffin ◽  
L. Vijaya Mohan Rao
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Protein C ◽  
Factor Viia ◽  
Vascular Endothelial Cell ◽  
Cell Protein ◽  
Mouse Strains ◽  
Biased Agonism ◽  
Protease Activated Receptor 1

Objective: Recent studies showed that FVIIa (factor VIIa), upon binding to EPCR (endothelial cell protein C receptor), elicits endothelial barrier stabilization and anti-inflammatory effects via activation of PAR (protease-activated receptor)-1–mediated signaling. It is unknown whether FVIIa induces PAR1-dependent cytoprotective signaling through cleavage of PAR1 at the canonical site or a noncanonical site, similar to that of APC (activated protein C). Approach and Results: Mouse strains carrying homozygous R41Q (canonical site) or R46Q (noncanonical site) point mutations in PAR1 (QQ41-PAR1 and QQ46-PAR1 mice) were used to investigate in vivo mechanism of PAR1-dependent pharmacological beneficial effects of FVIIa. Administration of FVIIa reduced lipopolysaccharide-induced inflammation, barrier permeability, and VEGF (vascular endothelial cell growth factor)-induced barrier disruption in wild-type (WT) and QQ46-PAR1 mice but not in QQ41-PAR1 mice. In vitro signaling studies performed with brain endothelial cells isolated from WT, QQ41-PAR1, and QQ46-PAR1 mice showed that FVIIa activation of Akt (protein kinase B) in endothelial cells required R41 cleavage site in PAR1. Our studies showed that FVIIa cleaved endogenous PAR1 in endothelial cells, and FVIIa-cleaved PAR1 was readily internalized, unlike APC-cleaved PAR1 that remained on the cell surface. Additional studies showed that pretreatment of endothelial cells with FVIIa reduced subsequent thrombin-induced signaling. This process was dependent on β-arrestin1. Conclusions: Our results indicate that in vivo pharmacological benefits of FVIIa in mice arise from PAR1-dependent biased signaling following the cleavage of PAR1 at the canonical R41 site. The mechanism of FVIIa-induced cytoprotective signaling is distinctly different from that of APC. Our data provide another layer of complexity of biased agonism of PAR1 and signaling diversity.

Polymorphisms in the endothelial protein C receptor gene and thrombophilia

2007 ◽  
Vol 98 (09) ◽  
pp. 564-569 ◽  
Author(s):  
Pilar Medina ◽  
Silvia Navarro ◽  
Amparo Estellés ◽  
Francisco España
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Protein C ◽  
Blood Clotting ◽  
Receptor Gene ◽  
Vascular Endothelial Cell ◽  
Activated Protein C ◽  
Vascular Endothelial ◽  
Endothelial Protein C Receptor ◽  
Clotting Cascade

SummaryThe protein C anticoagulant pathway plays a crucial role as a regulator of the blood clotting cascade. Protein C is activated on the vascular endothelial cell membrane by the thrombin-thrombomodulin complex. Once formed, activated protein C (APC) down-regulates thrombin formation by inactivating factors (F)Va and FVIIIa. Endothelial protein C receptor (EPCR) is able to bind protein C and increase the rate of protein C activation. Normal APC generation depends on the precise assemblage, on the surface of endothelial cells, of thrombin, thrombomodulin, protein C and EPCR.Therefore, any change in the efficiency of this assemblage may cause reduced/increased APC generation and modify the risk of thrombosis. This review highlights the different mutations/polymorphisms reported in the EPCR gene and their association with the risk of thrombosis.

Effect of angiotensin(1-7) on the expression of E-selectin induced by angiotensinII and its mechanism in vascular endothelial cell

2010 ◽  
Vol 34 (8) ◽  
pp. S71-S71
Author(s):  
Xiaohui Shen ◽  
Zhi‑Bin Wen ◽  
Na Li ◽  
Qingmei Cheng ◽  
Xiaofan He ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial

Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms

1995 ◽  
Vol 74 (04) ◽  
pp. 1045-1049 ◽  
Author(s):  
P Butthep ◽  
A Bunyaratvej ◽  
Y Funahara ◽  
H Kitaguchi ◽  
S Fucharoen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Immunosorbent Assay ◽  
Plasma Proteins ◽  
Clinical Symptoms ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Leg Ulcers

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.

Sign in / Sign up

Export Citation Format

Share Document