title: Enhanced protection against pulmonary hypertension with sildenafil and endothelial progenitor cell in rats.
abstract: BACKGROUND
  Sildenafil and bone marrow-derived endothelial progenitor cells (BMDEPCs) have been shown to ameliorate monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in the rat. We test whether combined sildenafil and BMDEPC treatment exerts additional protection against MCT-induced PAH in rats.
  
  
  METHODS
  Male Sprague-Dawley rats were randomized to receive saline injection only (group 1), MCT (70 mg/kg) only (group 2), MCT plus autologous BMDEPC (2.0×10(6) cells) transplantation (group 3), MCT with sildenafil (30 mg/kg/day) (group 4), and MCT with combined BMDEPCs-sildenafil (30 mg/kg/day) (group 5). Intravenous BMDEPC and oral sildenafil were given on day 3 after MCT administration. Hemodynamics were analyzed using Labchart software, whereas cellular and molecular parameters were measured using flow cytometry, real-time PCR, TUNEL assay, Western blot, and immunohistochemical staining.
  
  
  RESULTS
  By day 35 following MCT treatment, lower expression of connexin43, protein kinase C-ε, Bcl-2, and endothelial nitric oxide synthase and higher expression of tumor necrosis factor-α and caspase 3 were found in right ventricle (RV) and lung in group 2 compared with other groups (all p<0.05). The number of alveolar sacs and lung arterioles were also lower in group 2 than in other groups (all p<0.05). Furthermore, RV systolic pressure (RVSP), RV weight, and RV-to-final body weight ratio were substantially increased in group 2 than in other groups, and notably higher in groups 3 and 4 than in groups 1 and 5 (all p<0.0001).
  
  
  CONCLUSIONS
  Combined therapy with autologous BMDEPC and sildenafil is superior to either BMDPEC or sildenafil alone for preventing MCT-induced PAH.
authors.affiliation: Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Chun-Man
authors.initials: CM
authors.lastname: Yuen
authors.forename: Sarah
authors.initials: S
authors.lastname: Chua
authors.forename: Li-Teh
authors.initials: LT
authors.lastname: Chang
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Sheu
authors.forename: Fan-Yen
authors.initials: FY
authors.lastname: Lee
authors.forename: Morgan
authors.initials: M
authors.lastname: Fu
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D042783:Endothelial Cells / Q000637:transplantation*; D006976:Hypertension, Pulmonary / Q000517:prevention & control*; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D033581:Stem Cell Transplantation; D013450:Sulfones / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate