PMID- 10896252
OWN - NLM
STAT- MEDLINE
DCOM- 20001211
LR  - 20220224
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 83
IP  - 6
DP  - 2000 Jun
TI  - Heparin induces synthesis and secretion of tissue factor pathway inhibitor from 
      endothelial cells in vitro.
PG  - 937-43
AB  - TFPI is a potent inhibitor of the extrinsic coagulation system constitutively 
      synthesized by endothelial cells. A major portion of intravascular TFPI is stored 
      associated with endothelial cells. and administration of unfractionated heparin 
      (UFH) in vivo causes a prompt mobilization of TFPI into the circulation. The 
      present study was conducted to investigate how UFH affected the synthesis, 
      secretion and anticoagulant potency of TFPI in endothelial cells in vitro. A 
      spontaneously transformed immortal endothelial cell line was used (ECV304). 
      Stimulation of ECV304 cells with UFH caused a prompt dose-dependent (0-5 IU 
      UFH/ml) release of TFPI to the medium accompanied by no change of TFPI at the 
      surface membrane assessed by immunocytochemical methods. Northern blot analysis 
      revealed two mRNA transcripts for TFPI with a molecular size of 1.4 kb and 4.4 
      kb, respectively. Stimulation of ECV304 cells for 24 hrs with various 
      concentrations of UFH caused a dose-dependent increase of TFPI in the medium 
      (6.2-29.6 ng/10(6) cells within the concentration range 0-10 IU/ml). A similar 
      dose-dependent increase in the expression of both TFPI mRNA species was observed. 
      Long-term incubation of ECV304 cells with 5.0 IU/ml UFH caused a 5-10 fold 
      increase in the TFPI concentration accumulated in the medium over 48 hrs. The 
      increased TFPI mRNA expression induced by UFH appeared already after 10 min, 
      peaked after 2-4 hrs, remained augmented throughout the entire period of UFH 
      exposure, and preceded the synthesis-dependent increase in TFPI release by 2-4 
      hrs. The procoagulant activity of the cells was downregulated by 36% and the 
      contribution of TFPI to the anticoagulant potency of ECV304 cells was moderately 
      increased after 24 hrs heparin stimulation. It is suggested that these mechanisms 
      are of major importance for the anticoagulant function of heparins.
FAU - Hansen, J B
AU  - Hansen JB
AD  - Department of Medicine, Institute of Clinical Medicine, University of Tromso, 
      Norway. johnbh@fagmed.uit.no
FAU - Svensson, B
AU  - Svensson B
FAU - Olsen, R
AU  - Olsen R
FAU - Ezban, M
AU  - Ezban M
FAU - Osterud, B
AU  - Osterud B
FAU - Paulssen, R H
AU  - Paulssen RH
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Antibodies)
RN  - 0 (Anticoagulants)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Lipoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (lipoprotein-associated coagulation inhibitor)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Antibodies/pharmacology
MH  - Anticoagulants/metabolism/pharmacology
MH  - Cell Line
MH  - Culture Media, Conditioned/analysis/chemistry
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/cytology/*drug effects/metabolism
MH  - Fibrinolytic Agents/metabolism/pharmacology
MH  - Heparin/*pharmacology
MH  - Humans
MH  - Lipoproteins/biosynthesis/*drug effects/metabolism
MH  - RNA, Messenger/drug effects/metabolism
MH  - Thrombin/biosynthesis/drug effects
MH  - Time Factors
EDAT- 2000/07/15 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/07/15 11:00
PHST- 2000/07/15 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/07/15 11:00 [entrez]
AID - 00060937 [pii]
PST - ppublish
SO  - Thromb Haemost. 2000 Jun;83(6):937-43.