Simvastatin restores down-regulated GATA-6 expression in pulmonary hypertensive rats.
Vascular smooth muscle cell proliferation has been known to be predominant in vascular remodeling of pulmonary hypertensive. The GATA family proteins, a group of zinc finger transcription factors, play an important role during cell proliferation. The aim of present study was to investigate the expression of GATA-6 gene in experimental pulmonary hypertensive rats and explore the effect of regulation of GATA-6 expression by simvastatin on pulmonary vascular remodeling. The male Sprague-Dawley rats model was established with receiving pneumonectomy and monocrotaline (MCT) administration. Right pulmonary artery remodeling in these animals was compared with untreated rats or rats receiving simvastatin. The level of GATA-6 mRNA and protein expression was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Pneumonectomized, MCT-treated rats had significantly increased mean pulmonary arterial pressure (mPAP), RV/(LV + S) ratio (ratio of the right ventricular to left ventricular and septum weights), vascular occlusion scores (VOSs), and percent media wall thickness on day 35, all the indices were significantly decreased after simvastatin administration in these rats. The level of GATA-6 mRNA and protein were markedly decreased in these pneumonectomy and MCT-treated rats, and they were significantly up-regulated in these rats after receiving simvastatin. These results indicate that the development and progression of pulmonary hypertension is prevented by simvastatin by up-regulating GATA-6 expression in the lung tissue.
Liu
Bin
B
Department of Pediatric Cardiology, West China Second University Hospital, University, Chengdu, Sichuan, China.
Wang
Xiao-qin
XQ
Yu
Li
L
Zhou
Tong-fu
TF
Wang
Xian-min
XM
Liu
Han-min
HM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline; D011013:Pneumonectomy; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology*; D013997:Time Factors
D050993:GATA6 Transcription Factor; C084364:Gata6 protein, rat; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D016686:Monocrotaline; D019821:Simvastatin