title: Short-term exposure to low concentrations of thapsigargin inhibits replication of cultured human vascular smooth muscle cells.
abstract: BACKGROUND
  Central to the pathophysiology of stenosis following balloon angioplasty and arterial bypass surgery is proliferation of vascular smooth muscle cells (VSMCs). To investigate the role of calcium (Ca2+) in VSMC proliferation, the effect of thapsigargin, Ca2+ ionophore A23187, ionomycin, cyclopiazonic acid and di-tert-butylhydroquinone (all of which raise intracellular Ca2+ levels) on the proliferation of cultured human VSMCs was observed.
  
  
  METHODS
  Cultured VSMCs from human saphenous vein were treated with calcium-modulating drugs and proliferation was assessed by determining [3H]thymidine and 5-bromo-2'-deoxyuridine incorporation and cell number.
  
  
  RESULTS
  Over a 48-h exposure, thapsigargin inhibited VSMC replication (median 50 per cent maximal inhibitory concentration 2 nmol/l) whereas the other drugs were much less effective. Short-term exposure (5, 10, 30 and 60 min) to thapsigargin elicited a significant dose-dependent inhibition of VSMC replication whereas, again, the other drugs were without significant effect.
  
  
  CONCLUSIONS
  Thapsigargin-sensitive intracellular Ca2+ pools play a key role in controlling VSMC proliferation and specialized means of administering thapsigargin may constitute a possible approach to preventing stenosis.
authors.affiliation: University Department of Surgery, Royal Free Hospital and School of Medicine, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Shukla
authors.forename: J Y
authors.initials: JY
authors.lastname: Jeremy
authors.forename: P
authors.initials: P
authors.lastname: Nicholl
authors.forename: B
authors.initials: B
authors.lastname: Krijgsman
authors.forename: G
authors.initials: G
authors.lastname: Stansby
authors.forename: G
authors.initials: G
authors.lastname: Hamilton
mesh_terms: D000328:Adult; D000368:Aged; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D012501:Saphenous Vein; D019284:Thapsigargin / Q000494:pharmacology*; D014648:Varicose Veins / Q000601:surgery
chemical_list: D004791:Enzyme Inhibitors; D006873:Hydroquinones; D007211:Indoles; C019359:2,5-di-tert-butylhydroquinone; D000001:Calcimycin; D015759:Ionomycin; D019284:Thapsigargin; D002118:Calcium; C000543:cyclopiazonic acid