Effect of Small Hairpin RNA Targeting Endothelin-Converting Enzyme-1 in Monocrotaline-Induced Pulmonary Hypertensive Rats.
10.3346/jkms.2012.27.12.1507
- Author:
Jae Sung SON
1
;
Kwan Chang KIM
;
Bo Kyung KIM
;
Min Sun CHO
;
Young Mi HONG
Author Information
1. Department of Pediatrics, Konkuk University School of Medicine, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Hypertension, Pulmonary;
Monocrotaline;
Small Hairpin RNA;
Lentivirus;
Endothelin-Converting Enzyme;
RNA, Small Interfering
- MeSH:
Animals;
Aspartic Acid Endopeptidases/*antagonists & inhibitors/blood/genetics;
Body Weight;
Heart Ventricles/physiopathology;
Hypertension, Pulmonary/chemically induced/*enzymology/mortality;
Lentivirus/genetics;
Lung/anatomy & histology/metabolism/pathology;
Male;
Metalloendopeptidases/*antagonists & inhibitors/blood/genetics;
Monocrotaline/toxicity;
Pulmonary Artery/drug effects/physiopathology;
RNA, Small Interfering/*metabolism;
Rats;
Rats, Sprague-Dawley;
Receptor, Endothelin A/genetics/metabolism;
Survival Rate;
Tumor Necrosis Factor-alpha/metabolism;
Vascular Endothelial Growth Factor A/metabolism
- From:Journal of Korean Medical Science
2012;27(12):1507-1516
- CountryRepublic of Korea
- Language:English
-
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-alpha 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.
