0130 : Endoglin is a new partner involved in platelet – endothelium interactions: role in microvessel stability?

Abstract

Hereditary Hemorragic Telangectasia (HHT) is characterized by a bleeding tendency that is postulated to be a consequence of microvessel fragility. HHT type 1 patients present heterozygous mutations in the endoglin gene resulting in a loss of expression of membrane endoglin in their endothelial cells (EC), while platelets in these patients display normal functions in vitro . We have reported previously that endothelial endoglin is involved, via its RGD motif, in inflammation though integrin-mediated leukocyte adhesion and transmigration. We recently found that endoglin-haplodeficient mice ( Eng+/–) have significantly higher bleeding time than Eng+/+ animals, therefore, we haypothesized that endoglin may also act as an adhesion molecule via integrin recognition in the interaction between EC and platelets during hemostasis. Coating plastic wells with the extracellular domain of endoglin enhanced platelets adhesion to the wells under static condition and this interaction persist under flow condition. Similarly, platelets could adhere on confluent EC in an endoglin-mediated process, while the silencing of endoglin expression in EC, and the addition of soluble endoglin or of anti-endoglin antibodies, inhibited stable platelet adhesion to EC. Remarkably, platelets from Glanzmann's thrombasthenia patients lacking the€αIIbβ3 integrin were defective for adhesion on EC, wheras CHO cells, ectopically expressing the human αIIbβ3 integrin acquired the capacity to adhere on rat myoblast transfectants expressing human endoglin (L6E9-E), thus confirming the interaction between endoglin and the αIIbβ3 integrin. These results establish a new critical role for endoglin in integrin-mediated adhesion of platelets to endothelium and provide a better understanding on the cellular mechanisms involved in bleeding events occurring in HHT. The author hereby declares no conflict of interest