Abstract
Background: Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance leading to right ventricular failure. Chronic hypoxia is a risk factor for PH. Otherwise, end-stage renal disease treated by haemodialysis is a risk factor for PH that occurs in 40% of the patients. Most of these last patients are treated with human recombinant erythropoietin (EPO) because of anaemia. Involvement of EPO itself as causative agent of PH is a controversial issue.
Aims: We investigated if EPO could by itself recapitulate all hemodynamic and morphologic features of hypoxia-induced pulmonary hypertension at similar level of increased haematocrit. As a secondary endpoint, we investigated whether endothelial progenitor cells, mobilized and implied in PH due to chronic hypoxia, could also be involved in EPO-induced PH.
Methods: 1st group: mice were treated with recombinant human EPO in normoxia during 2 weeks. 2nd group: mice were exposed to 2 weeks of hypoxia (10%). Control mice were placed in normoxic conditions. Blood analysis, echocardiography, right ventricular pressure, heart and lung histology and blood circulating endothelial progenitor cells were assessed after 2 weeks.
Results: 2 weeks exogenous EPO treatment causes PH with an important increase in pulmonary and right ventricular pressure but without inducing right ventricle hypertrophy and pulmonary artery remodelling. EPO provoked an increase in the blood mobilization of endothelial progenitor cells at a similar extent than hypoxia.
Conclusions: EPO recapitulates hemodynamic features of hypoxia-induced pulmonary hypertension in mice. Similarly to this last disease, EPO mobilizes cells that trigger PH.
- Copyright ©the authors 2016
