254 Estrogen Receptor α expression in both endothelium and hematopoietic cells is required for the accelerative effect of estradiol on reendothelialization

ObjectivesAlthough reducing rates of restenosis, drug-eluting stents also impair endothelial healing, resulting in increased risk of thrombosis. Alternatively, inhibition of neointimal hyperplasia is favoured by acceleration of reendothelialization. We previously showed that E2 accelerates reendothelialization through Estrogen Receptor α (ERα) and we now aimed at defining the cellular targets of this action.Methods and ResultsThe respective roles of endothelial and hematopoietic cellular targets of E2 were investigated in a mouse carotid injury model, using “en face” confocal microscopy, to follow endothelium repair. Grafting ERα –/– mice with ERα +/+ bone marrow (BM) did not restore the accelerative effect of E2 on reendothelialization, demonstrating the necessary role of extrahematopoietic ERα. Using a cell-specific inactivation of ERα (Cre-lox recombination system), we showed that endothelial ER_ plays a pivotal role in the E2 action. Finally, in wild type mice grafted with ERα –/–, the regenerative effect of E2 was abolished, demonstrating that ERα-expressing hematopoietic cells are also concomitantly required.ConclusionsWe demonstrate that endothelial ERα plays a pivotal role in E2-mediated reendothelialization. However, endothelial targeting alone is not sufficient and the concomitant stimulation of BM ERα is absolutely required. This cooperation should be now taken into account in strategies aimed at optimizing in-stent reendothelialization