title: The effect of PS-341 on pulmonary vascular remodeling in high blood flow-induced pulmonary hypertension.
abstract: The aim of the present study was to investigate the effects of PS-341 on vascular remodeling in an experimental rat model of high blood flow-induced pulmonary arterial hypertension (PAH), as well as to elucidate its mechanisms of action. We established the PAH model by a surgical method that implanted a left-to-right shunt. Three days post-surgery, the animals were randomly assigned to 3 groups (n=15 in each group): sham-operated (control), shunt (model) and PS-341 (treated) groups. Eight weeks post-surgery, hemodynamic parameters were significantly improved in the PS-341 group compared with the shunt group (P<0.05). Immunohistochemical analysis indicated that the expression levels of ubiquitin and nuclear factor-κB (NF-κB) p65 were significantly higher in the shunt group compared with the sham-operated group (P<0.05). Semi-quantitative western blot analysis further confirmed that the levels of ubiquitin and NF-κB p65 were decreased, while those of IκB-α (an inhibitor of NF-κB) were significantly increased in the PS-341 group compared with the shunt group (P<0.05). In conclusion, PS-341 attenuates high blood flow-induced pulmonary artery remodeling in rats via inhibition of the NF-κB pathway.
authors.affiliation: Department of Pediatrics, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Zong-Shuai
authors.initials: ZS
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Luan
authors.forename: Mei
authors.initials: M
authors.lastname: Lin
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Zhu
authors.forename: Yu
authors.initials: Y
authors.lastname: Ma
authors.forename: Zhao-Hua
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Yi-Biao
authors.initials: YB
authors.lastname: Wang
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D065627:Familial Primary Pulmonary Hypertension; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000517:prevention & control; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000187:drug effects; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001897:Boronic Acids; D020672:I-kappa B Proteins; C000606206:Nfkbia protein, rat; D011719:Pyrazines; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D000069286:Bortezomib