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

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 E...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Clay T. Cohen, Nancy A. Turner, Joel L. Moake
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d01a3ed759cf449a94ca17689ed6637b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d01a3ed759cf449a94ca17689ed6637b
record_format	dspace
spelling	oai:doaj.org-article:d01a3ed759cf449a94ca17689ed6637b2021-11-14T12:20:59ZHuman endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation10.1038/s41598-021-01360-w2045-2322https://doaj.org/article/d01a3ed759cf449a94ca17689ed6637b2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01360-whttps://doaj.org/toc/2045-2322Abstract 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.Clay T. CohenNancy A. TurnerJoel L. MoakeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Clay T. Cohen Nancy A. Turner Joel L. Moake Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation
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.
format	article
author	Clay T. Cohen Nancy A. Turner Joel L. Moake
author_facet	Clay T. Cohen Nancy A. Turner Joel L. Moake
author_sort	Clay T. Cohen
title	Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation
title_short	Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation
title_full	Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation
title_fullStr	Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation
title_full_unstemmed	Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation
title_sort	human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d01a3ed759cf449a94ca17689ed6637b
work_keys_str_mv	AT claytcohen humanendothelialcellsandfibroblastsexpressandproducethecoagulationproteinsnecessaryforthrombingeneration AT nancyaturner humanendothelialcellsandfibroblastsexpressandproducethecoagulationproteinsnecessaryforthrombingeneration AT joellmoake humanendothelialcellsandfibroblastsexpressandproducethecoagulationproteinsnecessaryforthrombingeneration
_version_	1718429256643510272

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

Ejemplares similares