SCIENTIFIC SUBCOMMITTEE SESSION
6 July 2007 Palexpo, Geneva, Switzerland  

Vascular Biology

Chair: J-M. Freyssinet ( France)
Co-Chairs: M. Berndt ( Australia), F. Dignat-George ( France), J. Griffin (USA), I. Juhan-Vague (France), P. Newman (USA)

The session was divided into three parts, addressing key issues in vascular biology and related disorders. None of the three topics does specifically belong to the scope of ISTH, which emphasizes the efforts to be made to maintain a leadership in the field.

Regarding microparticles (MPs), the new feature emerging from several presentations was the incidence of MPs in several types of cancers (B. Furie, N. Mackman, A. Weltermann), and more particularly with respect to the presence of tissue factor (TF). In a context where the elevation of MPs has been widely documented in cardiovascular diseases (R. Nieuwland, Y. Ahn), this considerably reinforces their pathophysiologic significance and therefore highlights the need of methodologies for better determination and characterization. A first step was precisely proposed as the “MP chalenge” that would consist in the distribution of appropriate materials for the standardization of flow cytometry analysis (B. Furie, F. Dignat-George). Calibrated microbeads should enable to standardize instrument settings, then biological samples could be distributed provided shipment problems are solved with respect to specific national security regulations. The search for correlation with the procoagulant potential(s) of MPs could also be included. If the samples to be tested could be prepared by a single laboratory, pre-analytical conditions would not require particular attention at this stage. For feasibility purpose, suggestions and input from investigators interested in participating in this challenge are welcome, please contact Françoise Dignat-George at: Francoise.Dignat-George@mail.ap-hm.fr. Although it is generally agreed that MPs stem from the plasma membrane of stimulated or apoptotic cells, it has however to be kept in mind that MPs have still to be better defined, e.g. on standardized bases since their physical properties, and probably a proportion of associated biological effects, mainly depend on the method used for their isolation. This is the other main goal of this subcommittee because it is essential to avoid confusion of functions with respect to other membraneous vehicles such as exosomes.

Receptor shedding and shed receptors as plasma biomarkers of vascular injury was the second topic. The fate of three platelet receptors was reported, GPV (J. Clemetson), GPVI (B. Nieswandt, P. Smethurst) and semaphorin-4D (L. Brass). This underscores the significance of the platelet “sheddome” in pathology. Not only the shed receptors have to be considered by themselves but also the pathways associated with, or accounting for, the shedding process. For instance, GPVI can be released as a true soluble truncated form or as a probable full-length membrane protein in MPs, depending on the conditions of platelet activation. In case studies in patients show the value of these, and perhaps other, shed receptors as biomarkers, standardized ELISA methods based on the availability of appropriate antibodies could be proposed for diagnosis and/or for the assessment of treatment efficiency.

Circulating endothelial cells (CEC) are believed to reflect endothelium damage or degeneration whereas endothelial progenitor cells (EPC) are viewed with regenerative potential, at least in cardiovascular disorders knowing they can also be mobilized in tumor development. Regarding CEC, definition and markers appear consensual. There is a general agreement on CD146-dependent immunomagnetic separation as a reference method, and owing to cell scarcity, there is a trend to combine a first step of enrichment and flow cytometry (F. Sabatier, P. Goon). The situation is somewhat more confusing for EPC as there is no consensus on the definition itself and no appropriate methodologies taking function and phenotype into account (P. Gaussem, J. George, N. Saunders). Hence, definition of EPC constitutes an essential next goal for this subcommittee.

In summary, in its first year of existence, the Scientific Subcommittee on Vascular Biology has identified three main topics to be further investigated at methodological and standardization levels, the interest being demonstrated by the importance of the attendance with up to ~300-350 participants.