title: The sGC activator inhibits the proliferation and migration, promotes the apoptosis of human pulmonary arterial smooth muscle cells via the up regulation of plasminogen activator inhibitor-2.
abstract: BACKGROUND
  Different types of pulmonary hypertension (PH) share the same process of pulmonary vascular remodeling, the molecular mechanism of which is not entirely clarified by far. The abnormal biological behaviors of pulmonary arterial smooth muscle cells (PASMCs) play an important role in this process.
  
  
  OBJECTIVE
  We investigated the regulation of plasminogen activator inhibitor-2 (PAI-2) by the sGC activator, and explored the effect of PAI-2 on PASMCs proliferation, apoptosis and migration.
  
  
  METHODS
  After the transfection with PAI-2 overexpression vector and specific siRNAs or treatment with BAY 41-2272 (an activator of sGC), the mRNA and protein levels of PAI-2 in cultured human PASMCs were detected, and the proliferation, apoptosis and migration of PASMCs were investigated.
  
  
  RESULTS
  BAY 41-2272 up regulated the endogenous PAI-2 in PASMCs, on the mRNA and protein level. In PAI-2 overexpression group, the proliferation and migration of PASMCs were inhibited significantly, and the apoptosis of PASMCs was increased. In contrast, PAI-2 knockdown with siRNA increased PASMCs proliferation and migration, inhibited the apoptosis.
  
  
  CONCLUSIONS
  PAI-2 overexpression inhibits the proliferation and migration and promotes the apoptosis of human PASMCs. Therefore, sGC activator might alleviate or reverse vascular remodeling in PH through the up-regulation of PAI-2.
authors.affiliation: Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongti South Rd, Beijing, PR China; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, 8 Gongti South Rd, Beijing, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Institute of Geriatrics, Beijing Hospital, 1 Dahua Rd, Beijing, PR China; National Clinical Research Center for Respiratory Diseases, 1 Dahua Rd, Beijing, PR China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Zou
authors.affiliation: Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongti South Rd, Beijing, PR China; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, 8 Gongti South Rd, Beijing, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongti South Rd, Beijing, PR China; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, 8 Gongti South Rd, Beijing, PR China.
authors.forename: Yuanhua
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongti South Rd, Beijing, PR China; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, 8 Gongti South Rd, Beijing, PR China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Zhai
authors.affiliation: Institute of Geriatrics, Beijing Hospital, 1 Dahua Rd, Beijing, PR China; National Clinical Research Center for Respiratory Diseases, 1 Dahua Rd, Beijing, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongti South Rd, Beijing, PR China; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, 8 Gongti South Rd, Beijing, PR China; National Clinical Research Center for Respiratory Diseases, 1 Dahua Rd, Beijing, PR China. Electronic address: chenwangcjfh@163.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020536:Enzyme Activators / Q000494:pharmacology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D000959:Antihypertensive Agents; D001565:Benzoates; D020536:Enzyme Activators; D017396:Plasminogen Activator Inhibitor 2; D011720:Pyrazoles; D011725:Pyridines; C480588:BAY 58-2667
keywords: Apoptosis; Migration; Plasminogen activator inhibitor-2; Proliferation; Pulmonary arterial smooth muscle cells; Soluble guanylate cyclase