Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes

Author(s):  
Stefan Heinz ◽  
Joris Braspenning
Author(s):  
Christine Biron-Andréani ◽  
Edith Raulet ◽  
Lydiane Pichard-Garcia ◽  
Patrick Maurel

1987 ◽  
Author(s):  
H J Hassan ◽  
A Leonardi ◽  
C Chelucci ◽  
R Guerriero ◽  
P M Mannucci ◽  
...  

We have analyzed the expression of several blood coagulation factors (IX, VIII, X, fibrinogen chains) and inhibitors (antithrombin III, protein C) in human embryonic and fetal livers, obtained from legal abortions at 6-11 week post-conception. The age was established by morphologic staging and particularly crown-rump lenght measurement.Total cellular RNA was isolated from partially purified hepatocytes or total liver homogenate using the guanidine isothiocyanate method. Poly(A)+ RNA was selected by oligodT cellulose chromatography. The size and the number of the embryonic and fetal transcripts are equivalent to those observed in adult liver, as evaluated by Northern blot analysis of total or poly(A)+ RNA hybridized to human cDNA probes.The level of coagulation factor transcripts in embryonic and fetal liver was evaluated by dot hybridization of total RNA (0.5-10 ug), as compared to RNA extracted from normal adult liver biopsies. The expression of blood coagulation factors in embryos is generally reduced for all factors, but at a different degree. In 5-11 wk liver, the level of factor IX is 5-10% of that observed in adults, while fibrinogen, protein C, antithrombin III RNA level rises from 25 to 50% and factor X is expressed at a level comparable to that observed in adult liver.We conclude that during these stages of development blood coagulation factors are expressed according to three different time, curves, possibly due to the effect of different types of regulatory mechanisms.


1981 ◽  
Vol 90 (5) ◽  
pp. 1387-1395 ◽  
Author(s):  
Yasuo OHNO ◽  
Hisao KATO ◽  
Takashi MORITA ◽  
Sadaaki IWANAGA ◽  
Katsumi TAKADA ◽  
...  

2007 ◽  
Vol 92 (11) ◽  
pp. 4352-4358 ◽  
Author(s):  
Guenther Boden ◽  
Vijender R. Vaidyula ◽  
Carol Homko ◽  
Peter Cheung ◽  
A. Koneti Rao

Abstract Context: Type 2 diabetes mellitus (T2DM) is a hypercoagulable state. Tissue factor (TF) is the principal initiator of blood coagulation. Objective: Our objective was to examine the effects of hyperglycemia and hyperinsulinemia on the TF pathway of blood coagulation in T2DM. Design: Three study protocols were used: 1) acute correction of hyperglycemia (with iv insulin) followed by 24 h of euglycemia, 2) 24 h of selective hyperinsulinemia, and 3) 24 h of combined hyperinsulinemia and hyperglycemia. Setting: The study took place at a clinical research center. Study Participants: Participants included 18 T2DM patients and 22 nondiabetic controls. Results: Basal TF-procoagulant activity (TF-PCA), monocyte TF mRNA, plasma coagulation factor VII (FVIIc), and thrombin-anti-thrombin complexes were higher in T2DM than in nondiabetic controls, indicating a chronic procoagulant state. Acutely normalizing hyperglycemia over 2–4 h resulted in a small (∼7%) but significant decline in TF-PCA with no further decline over 24 h. Raising insulin levels alone raised TF-PCA by 30%, whereas raising insulin and glucose levels together increased TF-PCA (by 80%), thrombin-anti-thrombin complexes, and prothrombin fragment 1.2. Plasma FVIIa and FVIIc declined with increases in TF-PCA. Conclusion: We conclude that the combination of hyperglycemia and hyperinsulinemia, common in poorly controlled patients with T2DM, contributes to a procoagulant state that may predispose these patients to acute cardiovascular events.


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