Abstract 5481: Heparanase Regulates the Thrombotic Potential of Vascular Injury and Stent Placement
Abstract only Background: Heparanase cleaves heparan sulfate proteoglycans (HSPGs), key components of the extracellular matrix and critical endothelial mediators of hemostasis. Methods: Mice transgenic for human heparanase were used to evaluate the influence of heparanase overexpression on thrombosi...
Saved in:
| Published in: | Circulation (New York, N.Y.) Vol. 120; no. suppl_18 |
|---|---|
| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
03-11-2009
|
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract only
Background:
Heparanase cleaves heparan sulfate proteoglycans (HSPGs), key components of the extracellular matrix and critical endothelial mediators of hemostasis.
Methods:
Mice transgenic for human heparanase were used to evaluate the influence of heparanase overexpression on thrombosis in an ex-vivo and in-vivo model. To evaluate thrombotic potential, a laser induced thrombosis model was used. Arterial injury was also performed prior to measuring thrombosis to examine the effects of light and heavy injury on thrombosis in the heparanase transgenic mice. A novel ex-vivo murine assay of stent thrombosis was performed in which mouse aortas were stented into a flow loop perfused with mouse blood.
Results:
In the absence of injury there was no difference in the time for formation of thrombosis in the wildtype (WT) and heparanase transgenic (HPA Tg) mice. However, in the presence of light injury or heavy injury thrombosis in HPA Tg mice occurred significantly faster than in WT mice (63.0 minutes vs. 41.8 minutes, p=.034). The prothrombotic phenotype of HPA Tg mice was masked when heparin was administered prior to injury (68.5 minutes vs. 69.2 minutes p=NS). Blood from HPA Tg mice increased stent thrombosis threefold versus WT in flow loops as measured by optical density (2.81 vs. 1.0 optical density, p=.023) and increased adherent platelets were found in electron microscopy.
Conclusions:
Increased arterial expression of heparanase leads to increased thrombosis in the injured artery. In particular, endovascular stenting induces injury and flow disturbance that exacerbated the thrombotic potential of blood with increased heparanase levels.
Figure 1.
Electron microscopy of stents exposed to WT and HPA Tg blood. |
|---|---|
| ISSN: | 0009-7322 1524-4539 |
| DOI: | 10.1161/circ.120.suppl_18.S1099-a |