title: Enalapril reduces proliferation and hyaluronic acid release in orbital fibroblasts.
abstract: BACKGROUND
  Orbital fibroblast proliferation and hyaluronic acid (HA) release are responsible for some of the clinical features of Graves' ophthalmopathy (GO). Thus, inhibition of these processes may be a possible therapeutic approach to this syndrome. Enalapril, a widely used antihypertensive drug, was found to have some inhibitory actions on fibroblast proliferation in cheloid scars in vivo, based on which we investigated its effects in primary cultures of orbital fibroblasts from GO patients and control subjects.
  
  
  METHODS
  Primary cultures of GO and control fibroblasts were treated with enalapril or with a control compound (lisinopril). Cell proliferation assays, lactate dehydrogenase release assays (as a measure of cell necrosis), apoptosis assays, and measurement of HA in the cell media were performed.
  
  
  RESULTS
  Enalapril significantly reduced cell proliferation in both GO and control fibroblasts. Because enalapril did not affect cell necrosis and apoptosis, we concluded that its effects on proliferation reflected an inhibition of cell growth and/or a delay in cell cycle. Enalapril significantly reduced HA concentrations in the media from both GO and control fibroblasts.
  
  
  CONCLUSIONS
  Enalapril has antiproliferative and HA suppressing actions in both GO and control fibroblasts. Clinical studies are needed to investigate whether enalapril has any effects in vivo in patients with GO.
authors.affiliation: Endocrinology, University of Pisa, Pisa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Botta
authors.forename: Simonetta
authors.initials: S
authors.lastname: Lisi
authors.forename: Claudio
authors.initials: C
authors.lastname: Marcocci
authors.forename: Stefano
authors.initials: S
authors.lastname: Sellari-Franceschini
authors.forename: Roberto
authors.initials: R
authors.lastname: Rocchi
authors.forename: Francesco
authors.initials: F
authors.lastname: Latrofa
authors.forename: Francesca
authors.initials: F
authors.lastname: Menconi
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Altea
authors.forename: Marenza
authors.initials: M
authors.lastname: Leo
authors.forename: Eleonora
authors.initials: E
authors.lastname: Sisti
authors.forename: Giamberto
authors.initials: G
authors.lastname: Casini
authors.forename: Marco
authors.initials: M
authors.lastname: Nardi
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Michele
authors.initials: M
authors.lastname: Marinò
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004656:Enalapril / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D049970:Graves Ophthalmopathy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D008954:Models, Biological; D009915:Orbit / Q000166:cytology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D006820:Hyaluronic Acid