title: Differential effects of intravenous anesthetics on PDGF-BB-induced vascular smooth muscle cell migration.
abstract: BACKGROUND
  Intravenous anesthetics are used during the perioperative and/or postoperative period in critically ill patients. Vascular smooth muscle cells (VSMCs) play important roles in vascular injury repair or restenosis after intervention. We previously reported that platelet-derived growth factor (PDGF)-BB induces VSMC migration via extracellular signal-regulated kinase (ERK) and Akt in a VSMC line, A10 cells. In the present study, we investigated the effects of intravenous anesthetics on PDGF-BB-induced VSMC migration and the mechanism.
  
  
  METHODS
  VSMCs migration was assessed using Boyden chamber, and phosphorylation of each protein kinase was analyzed by Western blotting.
  
  
  RESULTS
  Propofol or midazolam but not ketamine or dexmedetomidine suppressed PDGF-BB-induced A10 cells migration in a concentration-dependent manner. The suppressive effects on migration were observed also in human aortic smooth muscle cells. Propofol or midazolam did not affect phosphorylation of PDGF receptor β in A10 cells. Propofol or midazolam failed to affect PDGF-BB-induced phosphorylation of ERK or Akt. On the other hand, propofol or midazolam attenuated PDGF-BB-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), but did not affect phosphorylation of stress-activated protein kinase/c-Jun N-terminal kinase. Both ketamine and dexmedetomidine had no effect on the phosphorylation of p38 MAPK induced by PDGF-BB.
  
  
  CONCLUSIONS
  These results strongly suggest that propofol or midazolam inhibits VSMC migration by PDGF-BB via suppression of p38 MAPK activation. Propofol or midazolam may affect VSMC function in critically ill patients.
authors: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors: Miki
authors: M
authors: Iida
authors: Kumiko
authors: K
authors: Tanabe
authors: Osamu
authors: O
authors: Kozawa
authors: Hiroki
authors: H
authors: Iida
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008874:Midazolam / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018686:Anesthetics, Intravenous; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D008874:Midazolam; D015742:Propofol