Reduced expression of annexin A2 is associated with impaired cell surface fibrinolysis and venous thromboembolism
| Autor: | Katherine A. Hajjar, Mary M. Ruisi, Maria T. DeSancho, Neha Kumar, Huigen Chen, Hannah Fassel |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Plasmin medicine.medical_treatment Immunology Cell Down-Regulation 030204 cardiovascular system & hematology Biochemistry Tissue plasminogen activator Peripheral blood mononuclear cell Young Adult 03 medical and health sciences 0302 clinical medicine Internal medicine Fibrinolysis medicine Humans RNA Messenger Annexin A2 biology business.industry S100A10 Venous Thromboembolism Cell Biology Hematology Middle Aged Endothelial stem cell 030104 developmental biology Endocrinology medicine.anatomical_structure biology.protein Female business medicine.drug |
| Zdroj: | Blood. 137:2221-2230 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Reduced plasma fibrinolysis has been identified as a potential risk factor for venous thromboembolism (VTE), but the role of cell surface fibrinolysis in VTE is unknown. The annexin A2/S100A10 complex serves as a coreceptor for plasminogen and tissue plasminogen activator (tPA), augmenting plasmin generation by 60-fold on the endothelial cell surface. Several studies in both mice and humans support the concept that A2 regulates fibrin homeostasis and intravascular thrombosis in vivo. Here, we examined A2 protein expression and function in 115 adult subjects with VTE and 87 healthy controls. Using peripheral blood mononuclear cells as a surrogate for endothelial cells, we found a 41% mean decrease in cell surface tPA-dependent fibrinolytic activity in subjects who had a positive personal and family history of VTE but tested negative for known inherited thrombophilias (ITs). A2 protein was reduced on average by 70% and messenger RNA levels by 30%, but neither decrease correlated with anticoagulant therapy. Neither cell A2 protein nor cell surface plasmin generation correlated with plasma-based clot lysis times, suggesting that the plasma and cell surface fibrinolytic systems operate independently of one another. These data suggest that reduced expression of annexin A2 protein is associated with cell surface hypofibrinolysis and may represent a novel risk factor for IT. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|