Heparanase Regulates Thrombosis in Vascular Injury and Stent-Induced Flow Disturbance
Objectives The purpose of this study was to examine the role of heparanase in controlling thrombosis following vascular injury or endovascular stenting. Background The use of endovascular stents are a common clinical intervention for the treatment of arteries occluded due to vascular disease. Bot...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/91961 https://orcid.org/0000-0003-3159-8175 https://orcid.org/0000-0002-7832-7156 https://orcid.org/0000-0002-3285-7290 |
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| author | Baker, Aaron B. Kolachalama, Vijaya Bhasker Golomb, Mordechai Indolfi, Laura Spruell, Christopher Zcharia, Eyal Vlodavsky, Israel Edelman, Elazer R. Gibson, William J., Ph. D. Massachusetts Institute of Technology |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Baker, Aaron B. Kolachalama, Vijaya Bhasker Golomb, Mordechai Indolfi, Laura Spruell, Christopher Zcharia, Eyal Vlodavsky, Israel Edelman, Elazer R. Gibson, William J., Ph. D. Massachusetts Institute of Technology |
| author_sort | Baker, Aaron B. |
| collection | MIT |
| description | Objectives
The purpose of this study was to examine the role of heparanase in controlling thrombosis following vascular injury or endovascular stenting.
Background
The use of endovascular stents are a common clinical intervention for the treatment of arteries occluded due to vascular disease. Both heparin and heparan sulfate are known to be potent inhibitors of thrombosis. Heparanase is the major enzyme that degrades heparan sulfate in mammalian cells. This study examined the role of heparanase in controlling thrombosis following vascular injury and stent-induced flow disturbance.
Methods
This study used mice overexpressing human heparanase and examined the time to thrombosis using a laser-induced arterial thrombosis model in combination with vascular injury. An ex vivo system was used to examine the formation of thrombus to stent-induced flow disturbance.
Results
In the absence of vascular injury, wild type and heparanase overexpressing (HPA Tg) mice had similar times to thrombosis in a laser-induced arterial thrombosis model. However, in the presence of vascular injury, the time to thrombosis was dramatically reduced in HPA Tg mice. An ex vivo system was used to flow blood from wild type and HPA Tg mice over stents and stented arterial segments from both animal types. These studies demonstrate markedly increased thromboses on stents with blood isolated from HPA Tg mice in comparison to blood from wild type animals. We found that blood from HPA Tg animals had markedly increased thrombosis when applied to stented arterial segments from either wild type or HPA Tg mice.
Conclusions
Taken together, this study's results indicate that heparanase is a powerful mediator of thrombosis in the context of vascular injury and stent-induced flow disturbance. |
| first_indexed | 2024-09-23T16:00:44Z |
| format | Article |
| id | mit-1721.1/91961 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:00:44Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/919612022-10-02T05:42:24Z Heparanase Regulates Thrombosis in Vascular Injury and Stent-Induced Flow Disturbance Baker, Aaron B. Kolachalama, Vijaya Bhasker Golomb, Mordechai Indolfi, Laura Spruell, Christopher Zcharia, Eyal Vlodavsky, Israel Edelman, Elazer R. Gibson, William J., Ph. D. Massachusetts Institute of Technology Massachusetts Institute of Technology. Institute for Medical Engineering & Science Harvard University--MIT Division of Health Sciences and Technology Gibson, William J. Kolachalama, Vijaya Bhasker Indolfi, Laura Edelman, Elazer R. Objectives The purpose of this study was to examine the role of heparanase in controlling thrombosis following vascular injury or endovascular stenting. Background The use of endovascular stents are a common clinical intervention for the treatment of arteries occluded due to vascular disease. Both heparin and heparan sulfate are known to be potent inhibitors of thrombosis. Heparanase is the major enzyme that degrades heparan sulfate in mammalian cells. This study examined the role of heparanase in controlling thrombosis following vascular injury and stent-induced flow disturbance. Methods This study used mice overexpressing human heparanase and examined the time to thrombosis using a laser-induced arterial thrombosis model in combination with vascular injury. An ex vivo system was used to examine the formation of thrombus to stent-induced flow disturbance. Results In the absence of vascular injury, wild type and heparanase overexpressing (HPA Tg) mice had similar times to thrombosis in a laser-induced arterial thrombosis model. However, in the presence of vascular injury, the time to thrombosis was dramatically reduced in HPA Tg mice. An ex vivo system was used to flow blood from wild type and HPA Tg mice over stents and stented arterial segments from both animal types. These studies demonstrate markedly increased thromboses on stents with blood isolated from HPA Tg mice in comparison to blood from wild type animals. We found that blood from HPA Tg animals had markedly increased thrombosis when applied to stented arterial segments from either wild type or HPA Tg mice. Conclusions Taken together, this study's results indicate that heparanase is a powerful mediator of thrombosis in the context of vascular injury and stent-induced flow disturbance. 2014-12-01T17:28:03Z 2014-12-01T17:28:03Z 2012-04 2011-10 Article http://purl.org/eprint/type/JournalArticle 07351097 http://hdl.handle.net/1721.1/91961 Baker, Aaron B., William J. Gibson, Vijaya B. Kolachalama, Mordechai Golomb, Laura Indolfi, Christopher Spruell, Eyal Zcharia, Israel Vlodavsky, and Elazer R. Edelman. “Heparanase Regulates Thrombosis in Vascular Injury and Stent-Induced Flow Disturbance.” Journal of the American College of Cardiology 59, no. 17 (April 2012): 1551–1560. © 2012 American College of Cardiology Foundation https://orcid.org/0000-0003-3159-8175 https://orcid.org/0000-0002-7832-7156 https://orcid.org/0000-0002-3285-7290 en_US http://dx.doi.org/10.1016/j.jacc.2011.11.057 Journal of the American College of Cardiology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Baker, Aaron B. Kolachalama, Vijaya Bhasker Golomb, Mordechai Indolfi, Laura Spruell, Christopher Zcharia, Eyal Vlodavsky, Israel Edelman, Elazer R. Gibson, William J., Ph. D. Massachusetts Institute of Technology Heparanase Regulates Thrombosis in Vascular Injury and Stent-Induced Flow Disturbance |
| title | Heparanase Regulates Thrombosis in Vascular Injury and Stent-Induced Flow Disturbance |
| title_full | Heparanase Regulates Thrombosis in Vascular Injury and Stent-Induced Flow Disturbance |
| title_fullStr | Heparanase Regulates Thrombosis in Vascular Injury and Stent-Induced Flow Disturbance |
| title_full_unstemmed | Heparanase Regulates Thrombosis in Vascular Injury and Stent-Induced Flow Disturbance |
| title_short | Heparanase Regulates Thrombosis in Vascular Injury and Stent-Induced Flow Disturbance |
| title_sort | heparanase regulates thrombosis in vascular injury and stent induced flow disturbance |
| url | http://hdl.handle.net/1721.1/91961 https://orcid.org/0000-0003-3159-8175 https://orcid.org/0000-0002-7832-7156 https://orcid.org/0000-0002-3285-7290 |
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