title: Granulocyte colony-stimulating factor attenuates monocrotaline-induced pulmonary hypertension by upregulating endothelial progenitor cells via the nitric oxide system.
abstract: Granulocyte colony-stimulating factor (G-CSF) has exhibited efficacy at preventing the progression of pulmonary hypertension (PH); however, the exact mechanism is not completely clear. The aim of the present study was to assess whether this protective effect was mediated by the upregulation of circulating endothelial progenitor cells (EPCs) via the nitric oxide (NO) system. PH was induced in male Sprague-Dawley (SD) rats by the administration of a single subcutaneous injection of monocrotaline (MCT). The rats were treated with recombinant human G-CSF (rhG-CSF, 50 μg/kg/day) by subcutaneous injection from day five to day seven subsequent to the injection of MCT. Nω-nitro-L-arginine methyl ester (L-NAME, 4 mg/kg/day) was intragastrically administered in addition to rhG-CSF as a negative intervention. The changes in hemodynamics and histology, the number and function of circulating EPCs and the concentration of plasma NO were evaluated. With the occurrence of PH in the rat model, the number and function of circulating EPCs were demonstrated to be markedly downregulated. Moreover, a reduced plasma concentration of NO was observed, which was positively correlated with the number of circulating EPCs. Administration of rhG-CSF elevated the plasma level of NO, upregulated the number and function of circulating EPCs and effectively improved pulmonary hemodynamics and vascular reconstruction. Furthermore, the positive correlation between the levels of plasma NO and circulating EPCs was also observed in the rhG-CSF treatment group. However, the protective effect of rhG-CSF in PH was attenuated by L-NAME, which mediated the downregulation of NO and the EPCs. Thus, the present study suggests that G-CSF may attenuate the progression of MCT-induced PH by improving vascular injury repair mechanisms via the NO-mediated upregulation of EPCs.
authors.affiliation: Laboratory of Tissue Engineering and Stem Cells, Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China ; Department of Pediatrics, The General Hospital of Huabei Oil Field Company, Renqiu, Hebei 062552, P.R. China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Liu
authors.forename: Zhong-Dong
authors.initials: ZD
authors.lastname: DU
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Zhong-Chao
authors.initials: ZC
authors.lastname: Han
authors.forename: Zhi-Xu
authors.initials: ZX
authors.lastname: He
keywords: endothelial progenitor cells; granulocyte colony-stimulating factor; hemodynamics; model; nitric oxide; pulmonary hypertension