PMID- 10326760
OWN - NLM
STAT- MEDLINE
DCOM- 19990803
LR  - 20190727
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 94
IP  - 3
DP  - 1999 May 1
TI  - Evidence that heparin but not hirudin reduces PAI-1 expression in cultured human 
      endothelial cells.
PG  - 137-45
AB  - Heparin and other antithrombotic drugs besides their anticoagulant action could 
      have a profibrinolytic effect. We have analyzed the effect of unfractionated 
      heparin (UFH) and hirudin on PAI-1 gene expression in human umbilical vein 
      endothelial cells (HUVEC). Cells were stimulated with UFH (1 and 10 IU/ml) and 
      hirudin (20 and 100 TIU/ml). Samples were obtained before and 2, 6, and 24 hours 
      after stimulation. mRNA analysis was conducted by reverse transcription followed 
      by polymerase chain reaction, and PAI-1 antigen was determined by ELISA. Addition 
      of UFH (10 IU/ml) to HUVEC resulted in a decrease of PAI-1 mRNA at 6 hours (40% 
      reduction) and 24 hours (60% reduction) and PAI-1 antigen. Hirudin, however, did 
      not modify significantly the PAI-1 mRNA nor the inhibitor secretion. The addition 
      of UFH (10 or 100 IU/ml) to endotoxin-stimulated HUVEC also reduced the increased 
      PAI-1 mRNA and antigen secretion (45%), whereas no effect could be observed with 
      hirudin. Our results suggest that UFH, but not hirudin, by reducing the 
      endothelial expression of PAI-1 might have a profibrinolytic effect.
FAU - Orbe, J
AU  - Orbe J
AD  - Laboratory of Vascular Biology and Thrombosis, Haematology Service, School of 
      Medicine, University of Navarra, Pamplona, Spain.
FAU - Montes, R
AU  - Montes R
FAU - Zabalegui, N
AU  - Zabalegui N
FAU - Perez-Ruiz, A
AU  - Perez-Ruiz A
FAU - Paramo, J A
AU  - Paramo JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Endotoxins)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Hirudins)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Recombinant Proteins)
RN  - 9005-49-6 (Heparin)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
SB  - IM
MH  - Cells, Cultured
MH  - Endothelium, Vascular/*cytology/*metabolism
MH  - Endotoxins/pharmacology
MH  - Fetal Blood/cytology
MH  - Fibrinolytic Agents/pharmacology
MH  - Gene Amplification
MH  - Gene Expression/drug effects
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/chemistry/genetics
MH  - Heparin/*pharmacology
MH  - Hirudins/*pharmacology
MH  - Humans
MH  - Infant, Newborn
MH  - Plasminogen Activator Inhibitor 1/chemistry/*genetics/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Umbilical Veins
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - S0049-3848(98)00203-5 [pii]
AID - 10.1016/s0049-3848(98)00203-5 [doi]
PST - ppublish
SO  - Thromb Res. 1999 May 1;94(3):137-45. doi: 10.1016/s0049-3848(98)00203-5.