Quantitive And Functional Change Of Circulating Endothelial Progenitor Cells In Dogs With Dehydromonocrotaline-Induced Pulmonary Hypertension

Background and oberjective: Primary pulmonary hypertension(PPH) is a rare disorder of unknown etiology with pathological changes in precapillary pulmonary artery. Recently, Various evidence suggested that the status of endothelial progenitor cells(EPCs) may be involved in the progress of the disease, and the PPH patients get benefits from autological EPCs transplantation.The study try to observe the Quantitive and Functional Change of Circulating Endothelial Progenitor Cells in Dogs with Dehydromonocrotaline-Induced Pulmonary Hypertension. and provides the theory basis for autological EPCs transplantation for PPH treatment.Method: We induced canine PH model with dehydromonocrotaline methology, which resembles the human PPH conditions as well as possible. Circulating EPCs were enumerated as AC133+KDR+ cells by fluorescence-activated cell sorter(FACS) using counting beads, and the number and activity of EPCs after in vitro expansion were determined by acLDL uptake/lectin staining assay and in vitro tubule forming assay.Result: After six weeks of DHMC administration, all treated dogs had significant pulmonary hypertension (19.2±3.1mmHg vs. 11.2 ± 1.8mmHg, P<0.05) . A significant decrease was observed in circulating EPCs in PH condition compared with baseline (206.11 ± 26.78 cells/ml vs. 632.78 ± 42.78cells/ml, p<0.05), EPCs after expanded in vitro were also reduced in PH (41.33±5.85 vs. 22.44±6.44EPCs/x200 field; p<0.05).In addition, in vasculogenesis assay, PH EPCs formed less quantitative(11.22±2.77 vs. 21.11±2.76 tubules/x200 field, respectively, P<0.05) and less qualitive tubules than baseline EPCs.Conclusion: Our data demonstrate that EPC numbers and activity are impaired in DHMC induced-PH canine model. Given the great similarity of this model to human PPH and the important role of EPCsfor reendothelialization/neovascularization, it reflects the depletion ofEPCs in PPH and provides the theory basis for autological EPCstransplantation for PPH treatment.