title: Iptakalim influences the proliferation and apoptosis of human pulmonary artery smooth muscle cells.
abstract: The aim of the present study was to determine the effect of an ATP-sensitive K+ (KATP) channel opener iptakalim (IPT) on the proliferation and apoptosis of human pulmonary artery smooth muscle cells (HPASMCs), and examine the potential value of IPT to hypoxic pulmonary hyper-tension (HPH) at a cellular level. HPASMCs were divided into the control, ET-1, ET-1+IPT and ET-1+IPT+glibenclamide (GLI) groups. GLI was administered 30 min prior to ET-1 and IPT. The 4 groups were incubated with corresponding reagents for 24 h. Cell viability was evaluated using a CCK-8 assay, cell proliferation by 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, and cell apoptosis via the expression of apoptosis-related proteins, i.e., Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) using western blotting. We incubated HPASMCs with varying concentrations of ET-1 for 24, 48 and 72 h, and found that cell survival rate was increased in a dose-dependent manner (P<0.05) rather than in a time-dependent manner (P>0.05). After co-incubation of HPASMCs with varying concentrations of IPT and ET-1 for 24 h, the cell survival rate was decreased in a dose-dependent manner. The cell survival rate in the IPT+ET-1 group was significantly lower than that in the ET-1 group (P<0.05). The cell viability (P<0.05) and proliferation (P<0.05) in the ET-1 group were higher than those in the control group, and the expression of Bax/Bcl-2 was lower than the control group (P<0.05). The cell viability (P<0.05) and proliferation (P<0.05) in the ET-1+IPT group were lower than those in the ET-1 group, and the expression of Bax/Bcl-2 was higher than that in the ET-1 group (P<0.05). The cell viability (P<0.05) and proliferation (P<0.05) in the ET-1+IPT+GLI group were higher than those in the ET-1+IPT group, and the expression of Bax/Bcl-2 was lower than that in the ET-1+IPT group (P<0.05). In conclusion, IPT inhibited ET-1‑induced HPASMC proliferation and promoted cell apoptosis. Thus, it may play an important role in the treatment of HPH.
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011437:Propylamines; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein