Human endoglin as a potential new partner involved in platelet–endothelium interactions
Autor: | Carmelo Bernabeu, David M. Smadja, Consuelo González-Manchón, Christilla Bachelot-Loza, Dominique Pidard, Pascale Gaussem, Sonia Poirault-Chassac, Francisco J. Blanco, Jose Miguel López Novoa, Miguel Pericacho, Carmen Langa, Elisa Rossi |
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Přispěvatelé: | Ministerio de Economía y Competitividad (España), Centro de Investigación Biomédica en Red Enfermedades Raras (España), Instituto de Salud Carlos III, Red Española de Investigación Renal |
Rok vydání: | 2017 |
Předmět: |
TGF-β
Blood Platelets 0301 basic medicine Endothelium Integrin Inflammation CHO Cells Cell Communication Platelet Glycoprotein GPIIb-IIIa Complex HHT Cell Line 03 medical and health sciences Cellular and Molecular Neuroscience Cricetulus Thrombasthenia Bleeding time Cricetinae hemic and lymphatic diseases Cell Adhesion otorhinolaryngologic diseases medicine Animals Humans Platelet Molecular Biology Cells Cultured Mice Knockout Pharmacology RGD biology medicine.diagnostic_test Chemistry Endoglin Endothelial Cells Cell Biology CXCL12 Preeclampsia Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Hereditary hemorrhagic telangiectasia Hemostasis biology.protein Molecular Medicine Original Article medicine.symptom |
Zdroj: | Cellular and Molecular Life Sciences Digital.CSIC. Repositorio Institucional del CSIC instname |
ISSN: | 1420-9071 1420-682X |
Popis: | 16 p.-7 fig. Rossi. E. et al. 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. This work was supported by Grants from Ministerio de Economia y Competitividad of Spain (SAF2013-43421-R to C. B., SAF2013-45784-R to J. M. L.-N., and BFU2010-15237 to C. G.-M.), Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER; ISCIII-CB06/07/0038 and ER16PIAC707 to C. B.), Red de Investigacion Cooperativa en Enfermedades Renales (REDINREN to J. M. L.-N.), The Conny-Maeva Charitable Foundation (to D. M. S.), and Fundación Renal Iñigo Alvarez de Toledo to J. M. L.-N. CIBERER and REDINREN are initiatives of the Instituto de Salud Carlos III (ISCIII) of Spain supported by FEDER funds. |
Databáze: | OpenAIRE |
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