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UMR_S1140

Innovations thérapeutiques en hémostase

Eduardo ANGLES-CANO is M.D., Sc.D. Emeritus Director of Research at Inserm.

 

Fibrinolysis/proteolysis on biological surfaces: pathophysiological relevance in thrombus dissolution.

 

Fibrinolysis/proteolysis on biological surfaces: pathophysiological relevance in thrombus dissolution

With my graduate students and co-workers we are pioneer in the study of fibrinolytic microvesicles (MVs) as functional messengers of plasmin generation. Since plasminogen activation is a property not only of vascular cells but also of other cell types including epithelial and inflammatory cells, our working hypothesis is that MVs derived from cells that express plasminogen activators may generate, disseminate and transfer plasmin proteolytic activity (Blood, 2007). For instance, besides endothelial cells and leucocytes, neurons are able to release microvesicles bearing plasmin and tPA activity (Biochem J 2010). We have found that endothelial cell- and leucocyte-derived microvesicles bear the machinery necessary for plasmin formation including plasminogen activators and its receptors: tPA for endothelial MVs and the uPA/uPAR system for leukocyte MVs (Haematologica 2013).

 

Furthermore, we have discovered a new mechanism for plasmin formation that bypass the requirement for co-assembly of plasminogen and uPA on the same surface (Blood 2010). These heterotypic cell-to-cell (platelets/ monocytes; platelets/MPs), cell-to-matrix (leukocytes/fibrin), or MPs-to-matrix (MPs/fibrin) proteolytic cross-talk represents an alternative pathway for localized plasmin formation that may be relevant to processes implicating cell migration and MP dissemination, i. e. inflammation or angiogenesis. Finally, our data provide additional evidence for a novel role of MPs and platelets, as vectors that generate and propagate plasmin fibrinolytic and/or proteolytic activity, and could thereby constitute a pharmacologic tool.

 

Present day projects are:

 

The development of a new test for the measurement and characterization of MVs (ANR COCERP coparticipants: F. Toti (U de Strasbourg, C. Belle (U de Grenoble). Within this frame we will study the microvesiculation properties of human bone marrow Mesenchymal stem cells and the fibrinolytic activity of released MVs.

 

We are also studying the interaction neutrophil-platelets and the role of NETs in fibrinolysis in sepsis and cerebrovascular ischaemic disease.

 

 

Current fields of interest:

 

  • Microvesicles as messengers and actors of fibrinolytic and proteolytic activity
  • Fibrinolysis and proteolysis in inflammatory diseases
  • Microvesicles, fibrinolysis and NET transformation of PMN in ischaemic disease.

 

 

INSERM UMR_S1140

Innovations Thérapeutiques en Hémostase
Contact courriel

Faculté de Pharmacie de Paris

4, avenue de l'Observatoire

75270 Paris Cedex 06