Platelet protein S limits venous but not arterial thrombosis propensity by controlling coagulation in the thrombus
| Autor: | François Saller, Yasuhiro Matsumura, Tilman M. Hackeng, Luca Bologna, Maria Desiré Reina Caro, Laurent Burnier, Anne Angelillo-Scherrer, Anne C. Brisset, Vladimir Ermolayev, José A. Fernández, Claudia Quarroz, Raja Prince-Eladnani, Sara Calzavarini, John H. Griffin |
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| Přispěvatelé: | RS: Carim - B01 Blood proteins & engineering, Biochemie |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Blood Platelets medicine.medical_specialty Immunology INHIBITION 030204 cardiovascular system & hematology Biochemistry Fibrin Thrombosis and Hemostasis Protein S C4B-BINDING PROTEIN 03 medical and health sciences 0302 clinical medicine Thrombin Internal medicine medicine Humans Platelet Platelet activation Thrombus 610 Medicine & health Blood Coagulation C ANTICOAGULANT Venous Thrombosis RISK biology PLASMA Chemistry Thrombosis Cell Biology Hematology medicine.disease DEFICIENCY INDIVIDUALS 030104 developmental biology Endocrinology RETROSPECTIVE FAMILY COHORT Coagulation FACTOR-V biology.protein cardiovascular system THROMBOPHILIA Protein C Platelet factor 4 medicine.drug |
| Zdroj: | Blood, 135(22), 1969-1982. The American Society of Hematology Blood |
| ISSN: | 0006-4971 |
| DOI: | 10.1182/blood.2019003630 |
| Popis: | Anticoagulant protein S (PS) in platelets (PSplt) resembles plasma PS and is released on platelet activation, but its role in thrombosis has not been elucidated. Here we report that inactivation of PSplt expression using the Platelet factor 4 (Pf4)-Cre transgene (Pros1lox/loxPf4-Cre+) in mice promotes thrombus propensity in the vena cava, where shear rates are low, but not in the carotid artery, where shear rates are high. At a low shear rate, PSplt functions as a cofactor for both activated protein C and tissue factor pathway inhibitor, thereby limiting factor X activation and thrombin generation within the growing thrombus and ensuring that highly activated platelets and fibrin remain localized at the injury site. In the presence of high thrombin concentrations, clots from Pros1lox/loxPf4-Cre− mice contract, but not clots from Pros1lox/loxPf4-Cre+ mice, because of highly dense fibrin networks. Thus, PSplt controls platelet activation as well as coagulation in thrombi in large veins, but not in large arteries. |
| Databáze: | OpenAIRE |
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