title: Effect of small hairpin RNA targeting endothelin-converting enzyme-1 in monocrotaline-induced pulmonary hypertensive rats.
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 (ET(A)) were significantly decreased in the shRNA group in week 4. The protein levels of ET(A) 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.
authors.affiliation: Department of Pediatrics, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Son
authors.forename: Kwan Chang
authors.initials: KC
authors.lastname: Kim
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Kim
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Cho
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Hong
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D001835:Body Weight; D000072396:Endothelin-Converting Enzymes; D006352:Heart Ventricles / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000201:enzymology* / Q000401:mortality; D016086:Lentivirus / Q000235:genetics; D008168:Lung / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D016686:Monocrotaline / Q000633:toxicity; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D034741:RNA, Small Interfering / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D044022:Receptor, Endothelin A; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016686:Monocrotaline; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes