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Sildenafil improves long-term effect of endothelial progenitor cell-based treatment for monocrotaline-induced rat pulmonary arterial hypertension.
MedLine Citation:
PMID:  23321332     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
BACKGROUND AIMS: We hypothesized that the long-term therapeutic effect of combined sildenafil and bone marrow-derived endothelial progenitor cells (BMDEPCs) on monocrotaline (MCT)-induced rat pulmonary arterial hypertension (PAH) is superior to either treatment alone.
METHODS: Male Sprague-Dawley rats (n = 40) were equally divided into normal controls, MCT (65 mg/kg, subcutaneously) only, MCT + sildenafil (25 mg/kg/day, orally), MCT + BMDEPCs (2.0 × 10(6) autologous cells, intravenously) and MCT + sildenafil+ BMDEPCs. BMDEPCs and sildenafil were given on day 21 after MCT administration. Animals were sacrificed by day 90 after MCT administration.
RESULTS: The apoptotic (caspase 3, Bax) and inflammatory (tumor necrosis factor-α, matrix metalloproteinase-9) biomarkers in right ventricle and lung and pulmonary expressions of fibrotic biomarkers (transforming growth factor-β, p-Smad3) and connexin 43 protein were lower in monotherapy groups (i.e., MCT + sildenafil and MCT + BMDEPCs) and further decreased in normal controls and combined treatment groups (i.e., MCT + sildenafil + BMDEPCs) compared with untreated animals (i.e., MCT only) (all P < 0.01). Expressions of anti-fibrotic biomarkers (bone morphogenetic protein-2, p-Smad1/5) and numbers of alveolar sacs and arterioles in lung were higher in monotherapy groups and further increased in normal controls and combined treatment groups compared with untreated animals (all P < 0.005). In right ventricle, connexin 43 and α-myosin heavy chain (MHC) expressions were higher in the monotherapy groups and further elevated in normal controls and combined treatment groups compared with untreated animals, whereas β-MHC exhibited the opposite pattern (all P < 0.01). Right ventricular systolic pressure and weight were lower in the monotherapy animals and further reduced in normal controls and combined treatment groups compared with untreated animals (all P < 0.0001).
CONCLUSIONS: Combined therapy with BMDEPCs and sildenafil was superior to either treatment alone in attenuating rodent MCT-induced PAH.
Authors:
Chia-Hung Yen; Tzu-Hsien Tsai; Steve Leu; Yung-Lung Chen; Li-Teh Chang; Han-Tan Chai; Sheng-Ying Chung; Sarah Chua; Ching-Yen Tsai; Hsueh-Wen Chang; Sheung-Fat Ko; Cheuk-Kwan Sun; Hon-Kan Yip
Publication Detail:
Type:  Journal Article     Date:  2012-12-11
Journal Detail:
Title:  Cytotherapy     Volume:  15     ISSN:  1477-2566     ISO Abbreviation:  Cytotherapy     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100895309     Medline TA:  Cytotherapy     Country:  England    
Other Details:
Languages:  eng     Pagination:  209-23     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan.
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