Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation
| dc.citation.articleNumber | 21852 | en_US |
| dc.citation.journalTitle | Scientific Reports | en_US |
| dc.citation.volumeNumber | 11 | en_US |
| dc.contributor.author | Cohen, Clay T. | en_US |
| dc.contributor.author | Turner, Nancy A. | en_US |
| dc.contributor.author | Moake, Joel L. | en_US |
| dc.date.accessioned | 2021-12-02T15:09:29Z | en_US |
| dc.date.available | 2021-12-02T15:09:29Z | en_US |
| dc.date.issued | 2021 | en_US |
| dc.description.abstract | In a previous study, we reported that human endothelial cells (ECs) express and produce their own coagulation factors (F) that can activate cell surface FX without the additions of external proteins or phospholipids. We now describe experiments that detail the expression and production in ECs and fibroblasts of the clotting proteins necessary for formation of active prothrombinase (FV–FX) complexes to produce thrombin on EC and fibroblast surfaces. EC and fibroblast thrombin generation was identified by measuring: thrombin activity; thrombin–antithrombin complexes; and the prothrombin fragment 1.2 (PF1.2), which is produced by the prothrombinase cleavage of prothrombin (FII) to thrombin. In ECs, the prothrombinase complex uses surface-attached FV and γ-carboxyl-glutamate residues of FX and FII to attach to EC surfaces. FV is also on fibroblast surfaces; however, lower fibroblast expression of the gene for γ-glutamyl carboxylase (GGCX) results in production of vitamin K-dependent coagulation proteins (FII and FX) with reduced surface binding. This is evident by the minimal surface binding of PF1.2, following FII activation, of fibroblasts compared to ECs. We conclude that human ECs and fibroblasts both generate thrombin without exogenous addition of coagulation proteins or phospholipids. The two cell types assemble distinct forms of prothrombinase to generate thrombin. | en_US |
| dc.identifier.citation | Cohen, Clay T., Turner, Nancy A. and Moake, Joel L.. "Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation." <i>Scientific Reports,</i> 11, (2021) Springer Nature: https://doi.org/10.1038/s41598-021-01360-w. | en_US |
| dc.identifier.digital | s41598-021-01360-w | en_US |
| dc.identifier.doi | https://doi.org/10.1038/s41598-021-01360-w | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/111733 | en_US |
| dc.language.iso | eng | en_US |
| dc.publisher | Springer Nature | en_US |
| dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. | en_US |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_US |
| dc.title | Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation | en_US |
| dc.type | Journal article | en_US |
| dc.type.dcmi | Text | en_US |
| dc.type.publication | publisher version | en_US |
Files
Original bundle
1 - 1 of 1