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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.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Sun CK,Lin YC,Yuen CM,Chua S,Chang LT,Sheu JJ,Lee FY,Fu M,Leu S,Yip HK

doi

10.1016/j.ijcard.2011.05.002

subject

Has Abstract

pub_date

2012-12-15 00:00:00

pages

45-58

issue

1

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(11)00399-8

journal_volume

162

pub_type

杂志文章

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