Molecular Weight Dependent Tissue Factor Pathway Inhibitor Release by Heparin and Heparin Oligosaccharides

Ma, Qing
Tobu, Mahmut
Schultz, Christopher
Jeske, Walter
Hoppensteadt, Debra
Walenga, Jeanine
Cornelli, Umberto
Lee, John
Linhardt, Robert J.
Hanin, Israel
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Molecular Weight Dependent Tissue Factor Pathway Inhibitor Release by Heparin and Heparin Oligosaccharides, Q. Ma, M. Tobu, C. Schultz, W. Jeske, D. Hoppensteadt, J. Walenga, U. Cornelli, J. Lee, R. Linhardt, I. Hanin, J. Fareed, Thrombosis Research, 119, 653-661, 2007.
Heparin and low molecular weight heparins exert their vascular effects by mobilizing tissue factor pathway inhibitor (TFPI) from the vascular endothelium into the blood circulation. We compared the influence of molecular weight on the TFPI release by heparin and its fractions in a non-human primate model. Primates were treated with unfractionated heparin, a low molecular weight heparin (gammaparin), or a heparin-derived oligosaccharide mixture (C3). Endothelial TFPI release was determined using both immunologic and functional assays. After intravenous administration, all agents significantly increased TFPI levels (p<0.05) in a dose dependent manner. The increase produced by unfractionated heparin and gammaparin was greater than that by C3 at an equal dosage (p<0.05). With subcutaneous injection, all agents produced less TFPI release. Repeated administration of heparin-derived oligosaccharides gradually increased TFPI release. A 1.89 fold increase in TFPI levels was observed 4 days after C3 treatment (2.5 mg/kg). Our findings indicated that TFPI release is dependent on the molecular weight of heparin and its derivatives. Heparin oligosaccharides exert their vascular effects through increased TFPI release after long-term repeated administration.
Thrombosis Research, 119, 653-661
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Thrombosis Research
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