ArticleBlood2011
Activated protein C up-regulates procoagulant tissue factor activity on endothelial cells by shedding the TFPI Kunitz 1 domain.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Review
- PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Characterization of Skin Aging-Associated Secreted Proteins (SAASP) Produced by Dermal Fibroblasts Isolated from Intrinsically Aged Human Skin.The Journal of investigative dermatology · 2015Article
- Biology of tissue factor pathway inhibitor.Blood · 2014Review
- TFPI1 mediates resistance to doxorubicin in breast cancer cells by inducing a hypoxic-like response.PloS one · 2014Article
- Comparison of the inhibitory activities of human tissue factor pathway inhibitor (TFPI)α and TFPIβ.Journal of thrombosis and haemostasis : JTH · 2013Article
- Factor VII-activating protease promotes the proteolysis and inhibition of tissue factor pathway inhibitor.Arteriosclerosis, thrombosis, and vascular biology · 2012Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Thrombin and activated protein C (APC) signaling can mediate opposite biologic responses in endothelial cells. Given that thrombin induces procoagulant tissue factor (TF), we examined how TF activity is affected by APC. Exogenous or endogenously generated APC led to increased TF-dependent factor Xa activity. Induction required APC's proteolytic activity and binding to endothelial cell protein C receptor but not protease activated receptors. APC did not affect total TF antigen expression or the availability of anionic phospholipids on the apical cell membrane. Western blotting and cell surface immunoassays demonstrated that APC sheds the Kunitz 1 domain from tissue factor pathway inhibitor (TFPI). A TFPI Lys86Ala mutation between the Kunitz 1 and 2 domains eliminated both cleavage and the enhanced TF activity in response to APC in overexpression studies, indicating that APC up-regulates TF activity by endothelial cell protein C receptor-dependent shedding of the Kunitz 1 domain from membrane-associated TFPI. Our results demonstrate an unexpected procoagulant role of the protein C pathway that may have important implications for the regulation of TF- and TFPI-dependent biologic responses and for fine tuning of the hemostatic balance in the vascular system.
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Registered trials
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