Simulated Surface-Induced Thrombin Generation in a Flow Field
A computational model of blood coagulation is presented with particular emphasis on the regulatory effects of blood flow, spatial distribution of tissue factor (TF), and the importance of the thrombomodulin-activated protein C inhibitory pathway. We define an effective prothrombotic zone that extend...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/90263 |
| _version_ | 1826197072532996096 |
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| author | Jordan, S.W. Chaikof, Elliot L. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Jordan, S.W. Chaikof, Elliot L. |
| author_sort | Jordan, S.W. |
| collection | MIT |
| description | A computational model of blood coagulation is presented with particular emphasis on the regulatory effects of blood flow, spatial distribution of tissue factor (TF), and the importance of the thrombomodulin-activated protein C inhibitory pathway. We define an effective prothrombotic zone that extends well beyond the dimensions of injury. The size of this zone is dependent on the concentrations of all reactive species, the dimensions of TF expression, the densities of surface molecules, and the characteristics of the flow field. In the case of tandem sites of TF, the relationship between the magnitude of the effective prothrombotic zone and the interval distance between TF sites dictate the net response of the system. Multiple TF sites, which individually failed to activate the coagulation pathway, are shown to interact in an additive manner to yield a prothrombotic system. Furthermore, activation of the thrombomodulin-activated protein C pathway in the regions between sites of TF downregulate the thrombin response at subsequent TF sites. The implications of prothrombotic effects, which extend downstream beyond the discrete site of injury to interact with subsequent lesions are critical given the systemic nature of atherosclerotic disease. |
| first_indexed | 2024-09-23T10:42:22Z |
| format | Article |
| id | mit-1721.1/90263 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:42:22Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/902632022-09-30T22:22:50Z Simulated Surface-Induced Thrombin Generation in a Flow Field Jordan, S.W. Chaikof, Elliot L. Massachusetts Institute of Technology. Department of Biological Engineering Chaikof, Elliot L. A computational model of blood coagulation is presented with particular emphasis on the regulatory effects of blood flow, spatial distribution of tissue factor (TF), and the importance of the thrombomodulin-activated protein C inhibitory pathway. We define an effective prothrombotic zone that extends well beyond the dimensions of injury. The size of this zone is dependent on the concentrations of all reactive species, the dimensions of TF expression, the densities of surface molecules, and the characteristics of the flow field. In the case of tandem sites of TF, the relationship between the magnitude of the effective prothrombotic zone and the interval distance between TF sites dictate the net response of the system. Multiple TF sites, which individually failed to activate the coagulation pathway, are shown to interact in an additive manner to yield a prothrombotic system. Furthermore, activation of the thrombomodulin-activated protein C pathway in the regions between sites of TF downregulate the thrombin response at subsequent TF sites. The implications of prothrombotic effects, which extend downstream beyond the discrete site of injury to interact with subsequent lesions are critical given the systemic nature of atherosclerotic disease. National Institutes of Health (U.S.) (Grant DK069275) National Institutes of Health (U.S.) (Grant HL106018) National Institutes of Health (U.S.) (Grant HL083867) National Institutes of Health (U.S.) (Grant HL56819) 2014-09-22T17:22:02Z 2014-09-22T17:22:02Z 2011-07 2011-05 Article http://purl.org/eprint/type/JournalArticle 00063495 1542-0086 http://hdl.handle.net/1721.1/90263 Jordan, S.W., and E.L. Chaikof. “Simulated Surface-Induced Thrombin Generation in a Flow Field.” Biophysical Journal 101, no. 2 (July 2011): 276–286. © 2011 Biophysical Society en_US http://dx.doi.org/10.1016/j.bpj.2011.05.056 Biophysical Journal 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 | Jordan, S.W. Chaikof, Elliot L. Simulated Surface-Induced Thrombin Generation in a Flow Field |
| title | Simulated Surface-Induced Thrombin Generation in a Flow Field |
| title_full | Simulated Surface-Induced Thrombin Generation in a Flow Field |
| title_fullStr | Simulated Surface-Induced Thrombin Generation in a Flow Field |
| title_full_unstemmed | Simulated Surface-Induced Thrombin Generation in a Flow Field |
| title_short | Simulated Surface-Induced Thrombin Generation in a Flow Field |
| title_sort | simulated surface induced thrombin generation in a flow field |
| url | http://hdl.handle.net/1721.1/90263 |
| work_keys_str_mv | AT jordansw simulatedsurfaceinducedthrombingenerationinaflowfield AT chaikofelliotl simulatedsurfaceinducedthrombingenerationinaflowfield |