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Effect of small hairpin RNA targeting endothelin-converting enzyme-1 in monocrotaline-induced pulmonary hypertensive rats

Title
Effect of small hairpin RNA targeting endothelin-converting enzyme-1 in monocrotaline-induced pulmonary hypertensive rats
Authors
Son J.S.Kim K.C.Kim B.K.Cho M.-S.Hong Y.M.
Ewha Authors
홍영미조민선김관창
SCOPUS Author ID
홍영미scopus; 조민선scopus; 김관창scopus
Issue Date
2012
Journal Title
Journal of Korean Medical Science
ISSN
1011-8934JCR Link
Citation
vol. 27, no. 12, pp. 1507 - 1516
Indexed
SCI; SCIE; SCOPUS; KCI WOS scopus
Abstract
The purpose of this study was to investigate the therapeutic effects of small hairpin RNA (shRNA) targeting endothelin-converting enzyme (ECE) -1 in monocrotaline (MCT)-induced pulmonary hypertensive rats. Ninty-four Sprague-Dawley rats were divided into three groups: control (n = 24), MCT (n = 35) and shRNA (n = 35). Four-week survival rate in the shRNA group was significantly increased compared to that in the MCT group. The shRNA group showed a significant improvement of right ventricular (RV) pressure compared with the MCT group. The MCT and shRNA groups also showed an increase in RV/(left ventricle + septum) ratio and lung/body weight. Plasma endothelin (ET)-1 concentrations in the shRNA group were lower than those in the MCT group. Medial wall thickness of pulmonary arterioles were increased after MCT injection and was significantly decreased in the shRNA group. The number of intra-acinar muscular pulmonary arteries was decreased in the shRNA group. The mRNA expressions of ET-1 and ET receptor A (ETA) were significantly decreased in the shRNA group in week 4. The protein levels of ETA were decreased in the shRNA group in week 2. The protein levels of tumor necrosis factor-α and vascular endothelial growth factor were decreased in the shRNA group in week 4. In conclusion, the gene silencing with lentiviral vector targeting ECE-1 could be effective against hemodynamic, histopathological and gene expression changes in pulmonary hypertension. © 2012 The Korean Academy of Medical Sciences.
DOI
10.3346/jkms.2012.27.12.1507
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의과대학 > 의학과 > Journal papers
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