Inhibitory effect of C-reactive protein on the release of tissue factor pathway inhibitor from human endothelial cells: reversal by low molecular weight heparin.
OBJECTIVE
The effects of C-reactive protein (CRP) and low molecular weight heparin (LMWH) on the release of tissue factor pathway inhibitor (TFPI) from human umbilical vein endothelial cells (HUVECs) were examined.


METHODS
Confluent HUVECs were resuspended and plated in 48-well plates coated with fibronectin polymer. Cells were allowed to attach for 3 h; they were then washed, and fresh medium with or without CRP at different concentrations (0 to 20 ng/mL) was added. At 4 h, TFPI released in the medium was measured using a commercial TFPI ELISA kit for total TFPI antigen. In parallel assays, wells containing HUVECs and CRP were treated with tinzaparin at 1 mg/mL.


RESULTS
Data showed that CRP significantly inhibited TFPI release from HUVECs in a concentration-dependent manner. In contrast, LMWH increased endothelial TFPI release. The amount of endothelial TFPI released was dependent on the heparin molecular weight distribution, with minimal effect at 3000 Da and maximum at 8000 to 12,000 Da. LMWH effectively reversed the inhibitory effects of CRP on TFPI release from HUVECs.


CONCLUSIONS
These findings support the hypothesis that CRP may play a direct role in promoting a hypercoagulable state by decreasing the release of the natural anticoagulant TFPI, which can be counteracted by LMWH.
Mousa
S A
SA
The Pharmaceutical Research Institute and Albany College of Pharmacy, Albany, NY 12208, USA. mousas@acp.edu
D000925:Anticoagulants / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D008074:Lipoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000078222:Tinzaparin; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D000078222:Tinzaparin; D002097:C-Reactive Protein