title: Propofol increases angiotensin-converting enzyme 2 expression in human pulmonary artery endothelial cells.
abstract: OBJECTIVE
  Propofol, a widely used sedative-hypnotic agent for induction/maintenance of anesthesia and sedation of critically ill patients, reportedly has therapeutic potential for hypertension. Angiotensin-converting enzyme 2 (ACE2) is a promising therapeutic target for pulmonary arterial hypertension. In the present study, we explored the effect of propofol on ACE2 expression in human pulmonary artery endothelial cells (HPAECs).
  
  
  METHODS
  HPAECs were treated with propofol in different concentrations (1, 10, 20, 40 or 50 µmol/l) for different lengths of time (6, 12, 18, 24 or 30 h) with or without transcription inhibitor actinomycin D or phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002.
  
  
  RESULTS
  Propofol increased the ACE2 mRNA level in a dose- and time-dependent manner within 24 h. Propofol treatment dose-dependently increased the ACE2 protein level and the cell membrane ACE2 activity. Transcription inhibitor actinomycin D and PI3K inhibitor LY294002 abrogated the augmenting effect of propofol on the mRNA level of ACE2 in HPAECs.
  
  
  CONCLUSIONS
  Propofol enhances the ACE2 expression in HPAECs by increasing the transcription of ACE2 via a PI3K-dependent mechanism, which leads to increased ACE2 activity on the cell membrane. This study provides new insights into propofol's vascular protective effects as well as its therapeutic potential for pulmonary arterial hypertension.
authors.affiliation: Department of Anesthesiology, Second Xiangya Hospital, Changsha, PR China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Cao
authors.forename: Linyong
authors.initials: L
authors.lastname: Xu
authors.forename: Bosheng
authors.initials: B
authors.lastname: Huang
authors.forename: Lixiang
authors.initials: L
authors.lastname: Wu
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015742:Propofol / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000085962:Angiotensin-Converting Enzyme 2; D006993:Hypnotics and Sedatives; D007703:Peptidyl-Dipeptidase A; D019869:Phosphatidylinositol 3-Kinases; D015742:Propofol; D012333:RNA, Messenger; C000705307:ACE2 protein, human