RGD Reference Report - Sildenafil improves long-term effect of endothelial progenitor cell-based treatment for monocrotaline-induced rat pulmonary arterial hypertension. - Rat Genome Database

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Sildenafil improves long-term effect of endothelial progenitor cell-based treatment for monocrotaline-induced rat pulmonary arterial hypertension.

Authors: Yen, CH  Tsai, TH  Leu, S  Chen, YL  Chang, LT  Chai, HT  Chung, SY  Chua, S  Tsai, CY  Chang, HW  Ko, SF  Sun, CK  Yip, HK 
Citation: Yen CH, etal., Cytotherapy. 2013 Feb;15(2):209-23. doi: 10.1016/j.jcyt.2012.09.002. Epub 2012 Dec 11.
RGD ID: 8662411
Pubmed: PMID:23321332   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jcyt.2012.09.002   (Journal Full-text)

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 x 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-alpha, matrix metalloproteinase-9) biomarkers in right ventricle and lung and pulmonary expressions of fibrotic biomarkers (transforming growth factor-beta, 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 alpha-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 beta-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.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GJA1Humanpulmonary hypertension treatmentISOGja1 (Rattus norvegicus) RGD 
Gja1Ratpulmonary hypertension treatmentIEP  RGD 
Gja1Mousepulmonary hypertension treatmentISOGja1 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gja1  (gap junction protein, alpha 1)

Genes (Mus musculus)
Gja1  (gap junction protein, alpha 1)

Genes (Homo sapiens)
GJA1  (gap junction protein alpha 1)


Additional Information