FVIII regulates the molecular profile of endothelial cells: functional impact on the blood barrier and macrophage behavior
| العنوان: | FVIII regulates the molecular profile of endothelial cells: functional impact on the blood barrier and macrophage behavior |
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| المؤلفون: | Marie Cadé, Javier Muñoz-Garcia, Antoine Babuty, Louis Paré, Denis Cochonneau, Karim Fekir, Mathias Chatelais, Marie-Françoise Heymann, Anna Lokajczyk, Catherine Boisson-Vidal, Dominique Heymann |
| المصدر: | Cellular and Molecular Life Sciences. 79 |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Pharmacology, Cell Membrane Permeability, Factor VIII, Proteome, Macrophages, Neovascularization, Physiologic, Cell Biology, Cellular and Molecular Neuroscience, Cell Movement, Cell Adhesion, Humans, Molecular Medicine, Endothelium, Vascular, Transcriptome, Molecular Biology |
| الوصف: | Hemophilia A is an inherited X-linked recessive bleeding disorder caused by deficient activity of blood coagulation factor VIII (FVIII). In addition, hemophilia patients show associated diseases including osteopenia, altered inflammation and vascular fragility which may represent the consequence of recurrent bleeding or may be related to the direct FVIII deficiency. 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 activated endothelium and transendothelial migration. By regulating vascular permeability plus leukocyte adhesion and transendothelial migration, the present work highlights new biological functions for FVIII. |
| تدمد: | 1420-9071 1420-682X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2519e0eb99b3337746abf535b0a8627eTest https://doi.org/10.1007/s00018-022-04178-5Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....2519e0eb99b3337746abf535b0a8627e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14209071 1420682X |
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