title: Raloxifene increases the capacity of serum to promote prostacyclin release in human endothelial cells: implication of COX-1 and COX-2.
abstract: OBJECTIVE
  Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase in endothelium. The aim of this study was to investigate the effect of serum from postmenopausal women treated with raloxifene on prostacyclin production by human umbilical vein endothelial cells and on cyclooxygenases-1 and -2.
  
  
  METHODS
  Serum was collected from 21 women receiving 60 mg/day of raloxifene, at baseline and at 3 and 6 months. Human umbilical vein endothelial cells were exposed to serum for 24 hours, and prostacyclin production was evaluated in supernatants. Selective inhibitors of cyclooxygenases-1 and -2 (SC-560 and NS-398) were used to investigate the relative contribution of each enzyme. Protein expression for each enzyme was determined using Western blot assays.
  
  
  RESULTS
  Prostacyclin production was increased by 30% (P < or = 0.001) when serum from women treated for 3 and 6 months was added. SC-560 reversed prostacyclin production but did not change baseline values. NS-398, in turn, reduced prostacyclin production using sera from baseline, 3 and 6 months. Cyclooxygenases-1 and -2 protein expression remained unaltered at each treatment step.
  
  
  CONCLUSIONS
  Serum from women treated with raloxifene stimulated prostacyclin release from human umbilical vein endothelial cells in culture, an effect that seems mediated by increased cyclooxygenase-1 activity.
authors.affiliation: Department of Pediatrics, Obstetrics and Gynaecology, University of Valencia, Av. Blasco Ibañez 17, E-46010 Valencia, Spain.
authors.forename: Pilar J
authors.initials: PJ
authors.lastname: Oviedo
authors.forename: Carlos
authors.initials: C
authors.lastname: Hermenegildo
authors.forename: Antonio
authors.initials: A
authors.lastname: Cano
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000502:physiology*; D008565:Membrane Proteins; D008875:Middle Aged; D009578:Nitrobenzenes / Q000494:pharmacology; D017698:Postmenopause / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D014471:Umbilical Veins / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011720:Pyrazoles; C115461:SC 560; D020845:Selective Estrogen Receptor Modulators; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D020849:Raloxifene Hydrochloride; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases