Functional impairment of endothelial colony forming cells in patients with idiopathic thromboembolic events

Endothelial progenitor cells (EPCs) are a rare population of bonemarrow derived cells playing a crucial role in adult vasculogenesis and endothelial homeostasis. The integrity of vessel endothelial lining is essential to prevent thrombosis, as thrombi formation is triggered by denuded or damaged endothelium. Endothelial alterationsmay be involved in the pathogenesis of idiopathic thromboembolism (ITE) that occurs in absence of triggering circumstances. Therefore in this study we investigated whether circulating EPCs isolated from ITE patients show possible alterations that may reflect a perturbation of the endothelial compartment. EPCs, isolated and expanded ex vivo as endothelial colonyforming cells (ECFCs), were cultured from peripheral blood mononuclear cells (PBMCs) obtained from 16 ITE patients and 30 matched controls. Cultures were analyzed for efficiency of ECFC colony isolation, cell viability, cell growth, immunophenotype, cytokine production and in vitro vasculogenesis. ECFC colonies were isolated from ITE patients with the same efficiency as controls. However, ECFC colonies isolated from ITE patientswere smaller (p\0.005) and characterized by a higher rate of early mortality (p\0.005). Moreover, ECFCs from ITE patients were characterized by a lower cell proliferation rate (p\0.05) and a reduced ability to form capillary-like structures in vitro (p\0.05) that were at least in part sustained by a lower production of IL-6 and IL-8 (p\0.05 in both cases). The results of this study demonstrate functional defects of ECFCs isolated and expanded from ITE patients, thus suggesting that ECFC characterization may represent a non-invasive tool to detect endothelial alterations and that EPCs may indeed contribute to hamper the maintenance of endothelial integrity and the physiologic antithrombotic function of endothelium in these patients.