Activation of plasminogen into plasmin at the surface of endothelial microparticles: a mechanism that modulates angiogenic properties of endothelial progenitor cells in vitro
| Autor: | Hélène Borghi, Stéphane Robert, Agnès Mialhe, Edouard Lamy, Agnès Basire, Eduardo Anglés-Cano, Romaric Lacroix, Victor Gurewich, Françoise Dignat-George, Laurent Plawinski, Florence Sabatier, Laurence Camoin-Jau, Ralph Pannell |
|---|---|
| Přispěvatelé: | Physiopathologie de l'Endothelium, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Vascular Research Laboratory, Beth Israel Deaconess - Harvard Medical School, Service de Microscopie Electronique, UFR de Médecine, Université de la Méditerranée - Aix-Marseille 2, Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm-Avenir/Lower-Normandy Regional Council grant |
| Rok vydání: | 2007 |
| Předmět: |
Plasmin
Angiogenesis Immunology Neovascularization Physiologic Inflammation urokinase Receptors Cell Surface [SDV.BC]Life Sciences [q-bio]/Cellular Biology 030204 cardiovascular system & hematology Biology Biochemistry endothelial microparticles Article Cell Line Receptors Urokinase Plasminogen Activator 03 medical and health sciences 0302 clinical medicine medicine Humans Fibrinolysin Progenitor cell 030304 developmental biology plasmin Tube formation 0303 health sciences Stem Cells Endothelial Cells Plasminogen Cell Biology Hematology Intracellular Membranes endothelial progenitors Molecular biology Urokinase-Type Plasminogen Activator Cell biology Urokinase receptor Endothelial stem cell Enzyme Activation medicine.symptom Plasminogen activator medicine.drug Protein Binding |
| Zdroj: | Blood Blood, American Society of Hematology, 2007, 110 (7), pp.2432-9. ⟨10.1182/blood-2007-02-069997⟩ |
| ISSN: | 0006-4971 1528-0020 |
| DOI: | 10.1182/blood-2007-02-069997⟩ |
| Popis: | 35 Pages Word counts : Total text: 4712. Abstract: 199 Françoise Dignat-George and Eduardo Angles-Cano are corresponding authors and share senior authorship for this study.; International audience; The regulation of plasmin generation on cell surfaces is of critical importance in the control of vascular homeostasis. Cell-derived microparticles participate in the dissemination of biological activities. However their capacity to promote plasmin generation has not been documented. In this study, we show that endothelial microparticles (EMP) from TNFalpha-stimulated endothelial cells, served as a surface for the generation of plasmin. The generation of plasmin involved expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) at the surface of EMP and was further increased by their ability to bind exogenous uPA on uPAR. Plasminogen was activated at the surface of EMP in a dose-dependent, saturable and specific manner as indicated by the inhibition of plasmin formation by epsilon-amino-caproic acid (epsilon-ACA) and carboxypeptidase B. EMP-induced plasmin generation affects tube formation mediated by endothelial progenitor cells. However, low amounts of EMP increased tube formation whereas higher concentrations inhibited it. Prevention of these effects by inhibitors of either uPA or plasmin, underscore the key role of EMP-induced plasmin generation. In conclusion, we demonstrated that EMP act as vectors supporting efficient plasmin generation and dissemination, a new pathway in the regulation of endothelial proteolytic activities with potential involvement in inflammation, angiogenesis and atherosclerosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|