Inserm, Institut national de la santé et de la recherche médicale
Faculté de pharmacie, Aix Marseille Université

Accueil » Le labo » Thématiques de recherche » Endothélium, thrombose et cancer » Mechanisms of thrombus formation

Mechanisms of thrombus formation

Grants from FRM (Programme Urgence Cardiovasculaire 2012-2015).

This project is currently performed by a PhD Student (R. Darbousset for the injury model), a Post Doctoral follow (Dr Grace Thomas, PhD) and an Associate Professor (Dr Corinne Frere, MD PhD).

The objective of this part is to characterize the involvement of circulating cells including PMNs and monocytes on both thrombus formation and thrombus stability in a mouse model of thrombus formation by real time digital intravital microscopy.

Our results indicate that PMNs interact with endothelial cells at a site of injury to induce activation of the coagulation cascade and formation of the thrombus. Indeed, we observed by digital real time intravital microscopy and laser-induced injury in living mice that PMN binding to the endothelial, via LFA-1/Icam-1 interactions, is a necessary step leading to activation of the tissue factor pathway (Darbousset R. et al. Blood, 2012).

We now determine how PMNs are activated in vivo following their interaction with the injured endothelial wall. We also observed that monocytes firmly bind latter at the site of injury, when fibrin starts to decreasing, suggesting an involvement of these cells in fibrinolysis. Stroke is a “thrombo-inflammatory” disorder that represents one of the most costly and long-term disabling conditions in adulthood worldwide. In vivo, platelets have been shown to contribute to infarct growth by participating in thrombus formation and by orchestrating inflammatory processes. We will use our model to extent what we observed in our model of injury in more relevant models of stroke.

Our goal will be to understand the involvement of circulating cells described in stroke (neutrophils, monocytes, T-cells) in thrombus formation and stability. The kinetics of accumulation and the relative roles of the different cellular partners will be identified and compared in all these different models of stroke.

Real time thrombus formation after a laser-induced injury

Calcium Mobilization into platelets participating to a growi

Main collaborations : Team 1, VCRM. Pr Sastre, Hospital La Timone, Marseille ; Pr Farge Bancel, Hospital St louis, Paris ; GFTC : Groupe Francophone Thrombose et Cancer : http://www.thrombose-cancer.com