Coronary diseases, thrombosis and haemostasis Inflammation, cardiovascular biomaterials

Specific cell adhesion molecules, or receptors, modulate the interactions of blood cells (leukocytes and platelets) with each other and with inflamed and damaged blood vessels; this process, in turn, contribute to initiate and progress various cardiovascular pathologies such as thrombosis, atherosclerosis, vasospasm, and restenosis.

We have demonstrated the importance of platelets in leukocyte adhesion to injured arteries and highlighted the contribution of the selectin family of cell adhesion molecules in these interactions. More specifically, we have revealed a central role for platelet P-selectin and its ligand leukocyte PSGL-1 in the thrombotic and restenotic process leading to vessel occlusion. Our research program aims to investigate the cellular mechanisms and pathways involved in the expression and function of p-selectin in platelet aggregation and in vessel remodelling.

Our strategy includes molecular and pharmacological approaches; these include in vitro experiments with isolated cells, as well as in vivo studies with animal models involving vascular injury by balloon dilation (angioplasty) to simulate various arterial pathologies in clinical practice.
This research is very important for many fundamental and clinical reasons.  Indeed, we intend to identify new mechanisms linking blood cells and damaged vessels, and to propose new therapeutic approaches to prevent vessel occlusion.

Relevant publications

Tanguay JF, Geoffry P, Sirois MG, Liberssan D, Kumar A, Schaub RG, Merhi Y. Prevention of in-stent restenosis via reduction of thrombo-inflammatory reactions with recombinant P-selectin glycoprotein ligand-1. Thrombosis and Haemostasis, 2004; 91:1186-1193

Libersan, D., Rousseau, G., Merhi Y.  Differential regulation of P-selectin expression by protein kinase A and G in thrombin-stimulated human platelets.
Thrombosis and Haemostasis, 2003; 89:310-317

Libersan, D., Merhi Y. Thrombin-induced platelet expression involves protein kinase C, but not protein tyrosine kinase or phosphoinositide 3-kinase activation.
Thrombosis and Haemostasis, 2003; 89:1016-1023

Caron, A, Théorêt, J.F., Mousa, S.A., Merhi Y. Antiplatelet effects of GPIIb/IIIa and P-selectin antagonism in platelet activation and binding to neutrophils.
J Cardiovasc Pharmacol, 2002; 40:296-306

Bienvenu, J.G., Tanguay, J.-F., Théorêt, J.F., Kumar, A., Schaub, R.G., Merhi Y. rPSGL-Ig reduces restenosis via inhibition of platelet neutrophil adhesion after double angioplasty in swine.
Circulation, 2001; 103:1128-1134

Théorêt, J.F., Bienvenu, J.G., Kumar, A., Merhi Y. P-selectin antagonism with recombinant P-selectin glycoprotein ligand-1 (rPSGL-Ig) inhibits circulating activated platelet binding to neutrophil induced by damaged arterial surfaces, J Pharmacol Expert Therap. 2001; 298:658-664