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Endogenous release of tissue factor pathway inhibitor by topical application of an ointment containing
D A Hoppensteadt1, J Fareed, P Raake
1Department of Pathology, Loyola University Chicago, 2160 S> First Avenue, Maywood, IL 60153, USA. dhoppen@lumc.edu
Abstract:
Several studies have shown that tissue factor pathway inhibitor (TFPI) is released after the intravenous and subcutaneous administration of heparin and heparin-related drugs. Mucopolysaccharide polysulfate (MPS) is a preparation of glycosaminoglycans (GAGS) derived from mammalian cartilage, which has several structural and functional properties similar to heparin. Previous reports have shown that MPS is capable of releasing TFPI after intravenous administration. Therefore, this investigation was performed to determine the ability of topically administered MPS to release TFPI in a nonhuman primate model. A group of four monkeys were administered 3% MPS ointment in a dosage of 0.5 g/kg corresponding to 15 mg MPS/kg; another four monkeys were administered placebo ointment at a dosage of 0.5 g/kg once a day for 5 days in a period of 10 days. No effect of MPS was observed on the coagulation assays activated partial thromboplastin time (APTT), thrombin time (TT) and Heptest or on the platelet count. However, both the total and free TFPI levels were significantly and progressively elevated over the 10-day period in comparison to the placebo control group (P<.05). It is proposed that the ability of the topically administered MPS to increase the free and total TFPI levels may be one of the modes of action that contributes to the anticoagulant and anti-inflammatory actions of this agent.
Insights
Topical mucopolysaccharide polysulfate (MPS) significantly increased tissue factor pathway inhibitor (TFPI) levels in nonhuman primates. This suggests a potential mechanism for MPS
Area of Science:
- Pharmacology and Toxicology
- Biochemistry and Molecular Biology
Background:
- Tissue factor pathway inhibitor (TFPI) release is a known effect of heparin administration.
- Mucopolysaccharide polysulfate (MPS), a glycosaminoglycan (GAG) preparation, shares structural and functional similarities with heparin.
- Previous studies indicate MPS can release TFPI following intravenous administration.
Purpose of the Study:
- To investigate the capacity of topically administered MPS to elicit TFPI release.
- To evaluate TFPI release in a nonhuman primate model following topical MPS application.
Main Methods:
- Nonhuman primates received either 3% MPS ointment or placebo ointment daily for 5 days over a 10-day period.
- Coagulation parameters (APTT, TT, Heptest) and platelet counts were monitored.
- Total and free TFPI levels were measured throughout the study period.
Main Results:
- Topical MPS administration did not affect standard coagulation assays or platelet counts.
- Both total and free TFPI levels were significantly and progressively elevated in the MPS group compared to placebo.
- The observed increase in TFPI levels persisted over the 10-day study duration.
Conclusions:
- Topically applied MPS effectively increases both total and free TFPI levels in a nonhuman primate model.
- This TFPI-releasing capability may represent a key mechanism underlying the anticoagulant and anti-inflammatory effects of MPS.
- Further research into topical MPS for its therapeutic potential is warranted.
