The effects of atorvastatin on pulmonary arterial hypertension and expression of p38, p27, and Jab1 in rats.
Statins have recently come under evaluation for the treatment of pulmonary arterial hypertension (PAH). The aim of this study was to examine the effects of atorvastatin on the clinical manifestations and expression of p38, p27 and Jab1 using a rat PAH model. Ninety-six male Wistar rats were divided into control (receiving no surgical treatment), vehicle and treatment groups, among which the last two groups underwent left pneumonectomy and were then treated with monocrotaline (MCT, 60 mg/kg). Both control and vehicle groups subsequently received saline, and the treatment group received atorvastatin (20 mg/kg) by stomach catheter. Rats were sacrificed, and mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. The expression of p38, p27, and Jab1 was evaluated by immunohistochemistry and Western blotting. At 28 days, mPAP and RVHI and expression levels of Jab1 and p38 in the vehicle group were significantly higher than those in the treatment and control groups. However, the expression of p27 was lowest in the vehicle group among the three groups. Atorvastatin reduced PAP and RVHI in the rat PAH model, decreased expression of p38 and Jab1 but increased expression of p27.
Gao
Yu-Fei
YF
Cardiovascular Department, First Affiliated Hospital of Harbin Medical University, Heilongjiang Province, P.R. China.
Zhu
Xiao-Duo
XD
Shi
Dong-Mei
DM
Jing
Zhi-Cheng
ZC
Li
Li
L
Ma
Dan
D
Fan
Zhi-Xin
ZX
Li
Jian
J
Wang
Yi-Wei
YW
Wu
Bing-Xiang
BX
D000818:Animals; D000069059:Atorvastatin; D000075686:COP9 Signalosome Complex; D005786:Gene Expression Regulation / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D016686:Monocrotaline; D011013:Pneumonectomy; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics*
C490121:Gps1 protein, rat; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D011758:Pyrroles; C413374:p27 antigen; D016686:Monocrotaline; D000069059:Atorvastatin; D048051:p38 Mitogen-Activated Protein Kinases; D000075686:COP9 Signalosome Complex