Oestrogen stimulates endothelial progenitor cells via oestrogen receptor-alpha

CONTEXT: Oestrogens play an important protective role on the vascular system. The endothelial cell layer is a direct target for these hormones, and expresses at least two oestrogen receptors, ER-alpha and ER-beta. Recent studies have shown that vascular healing is significantly modulated by circulating bone marrow-derived cells. A subset of these stem cells, endothelial progenitor cells (EPCs), have recently been described as a population of pluripotent cells within the peripheral blood capable of differentiating into endothelial cells. OBJECTIVE: In the present study we investigated the expression of ER-alpha and ER-beta on human EPCs and the effect that oestrogens have on the function of EPCs in vitro. METHODS: EPCs were isolated and cultured from healthy donors. RT-PCR, western blotting and immunohistochemistry were used to assess expression of ER-alpha and ER-beta. Proliferation and CFU assays were used to assess the response of EPCs to different doses of 17,beta-oestradiol. MAIN OUTCOME MEASURES: Expression of ER-alpha and ER-beta in EPCs, and the effect of 17,beta-oestradiol on proliferation of EPCs. RESULTS: Human EPCs express ER-alpha mRNA and protein. 17,beta-oestradiol increases proliferation of EPCs and CFU in a dose-dependent manner. CONCLUSIONS: Human EPCs express ER-alpha but not ER-beta, and oestrogens can stimulate the proliferation of these cells in vitro. Oestrogens exert these effects at concentrations that are usually reached during stimulation for in vitro fertilization in women, and therefore further studies are needed to clarify the clinical significance of these effects.