Enhanced protection against pulmonary hypertension with sildenafil and endothelial progenitor cell in rats.

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Title:	Enhanced protection against pulmonary hypertension with sildenafil and endothelial progenitor cell in rats.
Authors:	Sun CK;Lin YC;Yuen CM;Chua S;Chang LT;Sheu JJ;Lee FY;Fu M;Leu S;Yip HK
Date:	2011-05
Issue Date:	2012-09-05T07:42:15Z (UTC)
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 (70mg/kg) only (group 2), MCT plus autologous BMDEPC (2.0×10(6)cells) transplantation (group 3), MCT with sildenafil (30mg/kg/day) (group 4), and MCT with combined BMDEPCs-sildenafil (30mg/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.
Relation:	Int J Cardiol. 2011 May 25. [Epub ahead of print]
Appears in Collections:	[Department of Nursing] Papers

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