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Spatial propagation and localization of blood coagulation are regulated by intrinsic and protein C pathways, respectivelyстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
- Авторы: Panteleev Mikhail A., Ovanesov Mikhail V., Kireev Dmitrii A., Shibeko Aleksei M., Sinauridze Elena I., Ananyeva Natalya M., Butylin Andrey A., Saenko Evgueni L., Ataullakhanov Fazoil I.
- Журнал: Biophysical Journal
- Том: 90
- Номер: 5
- Год издания: 2006
- Издательство: Biophysical Society
- Местоположение издательства: United States
- Первая страница: 1489
- Последняя страница: 1500
- DOI: 10.1529/biophysj.105.069062
- Аннотация: Blood coagulation in vivo is a spatially nonuniform, multistage process: coagulation factors from plasma bind to tissue factor (TF)-expressing cells, become activated, dissociate, and diffuse into plasma to form enzymatic complexes on the membranes of activated platelets. We studied spatial regulation of coagulation using two approaches: 1), an in vitro experimental model of clot formation in a thin layer of plasma activated by a monolayer of TF-expressing cells; and 2), a computer simulation model. Clotting in factor VIII- and factor XI-deficient plasmas was initiated normally, but further clot elongation was impaired in factor VIII- and, at later stages, in factor XI-deficient plasma. The data indicated that clot elongation was regulated by factor Xa formation by intrinsic tenase, whereas factor IXa was formed by extrinsic tenase on activating cells and diffused into plasma, thus sustaining clot growth. Far from the activating cells, additional factor IXa was produced by factor XIa. Exogenously added TF had no effect on the clot growth rate, suggesting that plasma TF does not contribute significantly to the clot propagation process in a reaction-diffusion system without flow. Addition of thrombomodulin at 3-100 nM caused dose-dependent termination of clot elongation with a final clot size of 2-0.2 mm. These results identify roles of specific coagulation pathways at different stages of spatial clot formation (initiation, elongation, and termination) and provide a possible basis for their therapeutic targeting.
- Добавил в систему: Пантелеев Михаил Александрович