FVIII regulates the molecular profile of endothelial cells: functional impact on the blood barrier and macrophage behavior - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cellular and Molecular Life Sciences Année : 2022

FVIII regulates the molecular profile of endothelial cells: functional impact on the blood barrier and macrophage behavior

Le FVIII régule le profil moléculaire des cellules endothéliales : impact fonctionnel sur la barrière sanguine et le comportement des macrophages.

Résumé

Hemophilia A is an inherited X-linked recessive bleeding disorder caused by deficient activity of blood coagulation factor VIII (FVIII). In addition to a high risk of pathological bleeding, hemophilia patients show associated diseases including osteopenia, altered inflammation and vascular fragility. Nowadays, recombinant FVIII is proposed to treat hemophilia patients with no circulating FVIII inhibitor. Initially described as a coenzyme to factor IXa for initiating thrombin generation, there is emerging evidence that FVIII is involved in multiple biological systems, including bone, vascular and immune systems. The present study investigated: i) the functional activities of recombinant human FVIII (rFVIII) on endothelial cells, and ii) the impact of rFVIII activities on the functional interactions of human monocytes and endothelial cells. We then investigated whether rFVIII had a direct effect on the adhesion of monocytes to the endothelium under physiological flow conditions. We observed that direct biological activities for rFVIII in endothelial cells were characterized by: i) a decrease in endothelial cell adhesion to the underlying extracellular matrix; ii) regulation of the transcriptomic and protein profiles of endothelial cells; iii) an increase in the vascular tubes formed and vascular permeability in vitro; and iv) an increase in monocyte adhesion o activated endothelium and transendothelial migration. By regulating vascular permeability plus leukocyte adhesion and transendothelial migration, the present work highlights new biological functions for FVIII.
Fichier principal
Vignette du fichier
Cade et al Cell Mol Life Sci HAL.pdf (1.74 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03600694 , version 1 (27-10-2022)

Identifiants

Citer

Marie Cadé, Javier Muñoz-Garcia, Antoine Babuty, Louis Paré, Denis Cochonneau, et al.. FVIII regulates the molecular profile of endothelial cells: functional impact on the blood barrier and macrophage behavior. Cellular and Molecular Life Sciences, 2022, 79 (3), pp.145. ⟨10.1007/s00018-022-04178-5⟩. ⟨hal-03600694⟩
58 Consultations
89 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More