Prostacyclin therapy has markedly improved the outcome of patients with pulmonary hypertension (PH). Endothelial dysfunction is a key feature of PH, so the aim of our study was to determine how treprostinil contributes to the angiogenic functions of endothelial progenitors (ECFC). Treprostinil did not modify clonogenic properties nor endothelial differentiation potential from cord blood stem cells. Treprostinil treatment significantly increased the vessel-forming ability of ECFC combined with mesenchymal stem cells (MSC) in Matrigel implanted in nude mice. Silencing or blocking VEGF-A in MSC blocked the pro-angiogenic effect of treprostinil in vitro and in vivo. Clinical relevance was confirmed by the high level of VEGF-A detected in plasma from patients with pediatric pulmonary hypertension who had been treated with treprostinil. Our results suggest that VEGF-A level in patients could be a surrogate biomarker of treprostinil efficacy