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Cohen CT, Turner NA, Moake JL. Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation. Sci Rep. 2021;11(1):21852doi: 10.1038/s41598-021-01360-w.
Cohen, C. T., Turner, N. A., & Moake, J. L. (2021). Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation. Scientific reports, 11(1), 21852. https://doi.org/10.1038/s41598-021-01360-w
Cohen, Clay T, et al. "Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation." Scientific reports vol. 11,1 (2021): 21852. doi: https://doi.org/10.1038/s41598-021-01360-w
Cohen CT, Turner NA, Moake JL. Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation. Sci Rep. 2021 Nov 08;11(1):21852. doi: 10.1038/s41598-021-01360-w. PMID: 34750441; PMCID: PMC8575941.
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Sci Rep. 2021 Nov 08;11(1):21852. doi: 10.1038/s41598-021-01360-w.

Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation.

Scientific reports

Clay T Cohen, Nancy A Turner, Joel L Moake

Affiliations

  1. Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA. [email protected].
  2. Department of Bioengineering, Rice University, Houston, TX, USA.

PMID: 34750441 PMCID: PMC8575941 DOI: 10.1038/s41598-021-01360-w

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.

© 2021. The Author(s).

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