title: 5-Aminosalicylic Acid Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats by Increasing the Expression of Nur77.
abstract: The aim of this study is to investigate the effect of 5-aminosalicylic acid (5-ASA) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats and its molecular mechanism. Sixty male Sprague-Dawley rats (250-300 g) were evenly randomized into six groups: control group; PAH group induced by MCT intraperitoneal injection (50 mg/kg) on day 1; and four PAH groups treated for 30 days from day 2 with 5-ASA at 50 (5-ASA-50 group), 100 (5-ASA-100 group), 150 (5-ASA-150 group), and 200 mg/kg/day (5-ASA-200 group), respectively. Body mass, weight increment, survival rates, pulmonary artery pressure (PAP), right ventricular hypertrophy index (RVHI), and the signal pathway regulated by 5-ASA were assessed. (1) Compared with the control group, the PAH group had lower body mass and weight increment, and relative to the latter, 5-ASA-treated groups had larger body mass and weight increment except for groups 5-ASA-150 and 5-ASA-200 and greater overall survival rates; (2) SPAP, DPAP, MPAP, and RVHI in 5-ASA-treated groups, except for MPAP and RVHI in 5-ASA-200 group, were lower than those in the PAH group; (3) compared with the PAH group, Nur77 expression in the pulmonary arteries of 5-ASA-treated groups was increased; and (4) expression of inflammatory mediators (NF-κB p65) was lower, while that of IκBα was higher in the pulmonary arteries of 5-ASA-treated groups and control group than that in the PAH group (all P < 0.05). 5-ASA attenuates PAH in MCT-injected rats, reducing pulmonary arterial pressures and right ventricular hypertrophy and improving survival rates, via the Nur77-NF-κB/IκBα pathway involved in modulating the pulmonary vascular remodeling.
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, 200127, Shanghai, China.|Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
authors.forename: Ling-Yue
authors.initials: LY
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, 200127, Shanghai, China.
authors.forename: Zong-Ye
authors.initials: ZY
authors.lastname: Cai
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, 200127, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, 200127, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cardiology, Renji Hospital (South), School of Medicine, Shanghai Jiao Tong University, 2000 Jiangyue Road, 201112, Shanghai, China. dr_jyshen@sina.cn.
authors.forename: Jie-Yan
authors.initials: JY
authors.lastname: Shen
authors.affiliation: Department of Rheumatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, 200025, Shanghai, China. yangchengde@sina.com.
authors.forename: Cheng-de
authors.initials: CD
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, 200127, Shanghai, China.
authors.forename: Ben
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy; D008297:Male; D019804:Mesalamine / Q000494:pharmacology*; D016686:Monocrotaline / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D019804:Mesalamine; D016686:Monocrotaline
keywords: 5-aminosalicylic acid; MCT; Nur77; pulmonary arterial hypertension; pulmonary vascular remodeling