title: Simvastatin has beneficial effect on pulmonary artery hypertension by inhibiting NF-κB expression.
abstract: Whether Simvastatin has beneficial effect on pulmonary artery hypertension (PAH) remains unclear. This study aimed to explore the effect of simvastatin on PAH and the underlying mechanism. Male SD rats were randomized into three groups: control group, PAH model group, and treatment group with the intervention of the Simvastatin (n = 10, each group). Rat PVSMCs were isolated from pulmonary artery, cultured in vitro, and subjected to different treatment with PDGF, and/or Simvastatin or parthenolide. The mean pulmonary arterial pressure (mPAP), endomembrane proliferation in the pneumono-arteriole, and scores of the average angiemphraxis (VOS) were measured. The expression of NF-κB at mRNA and protein levels in the artery and PVSMCs was evaluated by fluorescent quantitative PCR, immunohistochemistry, and Western blot. Our results showed that mPAP, endomembrane proliferation in the pneumono-arteriole and VOS increased significantly in PAH model group compared with control group (P < 0.05). NF-κB expression was significantly higher in PAH model group than control group (P < 0.05), and also higher in the stimulated PVSMCs than control PVSMCs (P < 0.05). With the intervention of simvastatin, mPAP, endomembrane proliferation in the pneumono-arteriole and VOS decreased dramatically, compared with model group (P < 0.05). NF-κB expression was significantly decreased in both the artery and PVSMCs (P < 0.05). In conclusion, our study provides experimental evidence that NF-κB plays an important role in the occurrence of pulmonary artery hypertension and Simvastatin has beneficial effect on pulmonary artery hypertension by inhibiting the expression of NF-κB.
authors.affiliation: Department of Emergency, West China the Second Hospital of Sichuan University, Chengdu, 610041 Sichuan, China.
authors.forename: Zhong-Qiang
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Han-Min
authors.initials: HM
authors.lastname: Liu
mesh_terms: D000818:Animals; D001160:Arterioles / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011013:Pneumonectomy; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: D016328:NF-kappa B; D019821:Simvastatin