Human endoglin as a potential new partner involved in platelet-endothelium interactions

[EN] Complex interactions between platelets and activated endothelium occur during the thrombo-inflammatory reaction at sites of vascular injuries and during vascular hemostasis. The endothelial receptor endoglin is involved in inflammation through integrin-mediated leukocyte adhesion and transmigra...

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Detalles Bibliográficos
Autores: Rossi, Elisa, Pericacho Bustos, Miguel, Bachelot-Loza, Christilla, Pidard, Dominique, Gaussem, Pascale, Poirault-Chassac, Sonia, Blanco, Francisco J., Langa, Carmen, González-Manchón, Consuelo, López-Novoa, José M., Smadja, David M., Bernabeu, Carmelo
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/154604
Acceso en línea:http://hdl.handle.net/10366/154604
Access Level:acceso abierto
Palabra clave:Endoglin
Platelets
Endothelium
Hemostasis
Hereditary Hemorrhagic Telangiectasia
TGF-β
RGD
CXCL12
Preeclampsia
Cell Adhesion
Blood Platelets
Humans
Cells
Cricetulus
Cell Line
Cricetinae
Endothelial Cells
Cell Communication
Animals
CHO Cells
Mice
Platelet Glycoprotein GPIIb-IIIa Complex
humanos
ratones
comunicación celular
línea celular
adhesión celular
células CHO
células
animales
plaquetas
células endoteliales
complejo GPIIb-IIIa de glicoproteína plaquetaria
Descripción
Sumario:[EN] Complex interactions between platelets and activated endothelium occur during the thrombo-inflammatory reaction at sites of vascular injuries and during vascular hemostasis. The endothelial receptor endoglin is involved in inflammation through integrin-mediated leukocyte adhesion and transmigration; and heterozygous mutations in the endoglin gene cause hereditary hemorrhagic telangiectasia type 1. This vascular disease is characterized by a bleeding tendency that is postulated to be a consequence of telangiectasia fragility rather than a platelet defect, since platelets display normal functions in vitro in this condition. Here, we hypothesize that endoglin may act as an adhesion molecule involved in the interaction between endothelial cells and platelets through integrin recognition. We find that the extracellular domain of human endoglin promotes specific platelet adhesion under static conditions and confers resistance of adherent platelets to detachment upon exposure to flow. Also, platelets adhere to confluent endothelial cells in an endoglin-mediated process. Remarkably, Chinese hamster ovary cells ectopically expressing the human αIIbβ3 integrin acquire the capacity to adhere to myoblast transfectants expressing human endoglin, whereas platelets from Glanzmann's thrombasthenia patients lacking the αIIbβ3 integrin are defective for endoglin-dependent adhesion to endothelial cells. Furthermore, the bleeding time, but not the prothrombin time, is significantly prolonged in endoglin-haplodeficient (Eng +/-) mice compared to Eng +/+ animals. These results suggest a new role for endoglin in αIIbβ3 integrin-mediated adhesion of platelets to the endothelium, and may provide a better understanding on the basic cellular mechanisms involved in hemostasis and thrombo-inflammatory events.