title: [Effect of HMG-CoA reductase inhibition on endothelial dysfunction-inducing protein in hypercholesterolemic rabbits].
abstract: OBJECTIVE
  In our laboratory, we recently obtained evidence that cultured bovine endothelial cells contain cytosolic proteins that form complexes with the 3'-unstranslated region of endothelial nitric oxide synthase (eNOS) mRNA and are associated with its destabilization. The aim of this study was to determine the presence of such proteins and the level of eNOS expression in hypercholesterolemic rabbits as an in vivo model of endothelial dysfunction.
  
  
  RESULTS
  Endothelium-dependent relaxation in response to acetylcholine was reduced in aortic segments from hypercholesterolemic rabbits compared with controls. Treatment of hypercholesterolemic rabbits with simvastatin (25 mg/kg body weight/day) restored endothelium-dependent relaxation. Aortic eNOS expression was reduced in hypercholesterolemic rabbits and was accompanied by enhanced binding activity of a 60-KDa cytosolic protein and reduced stability of eNOS mRNA. Simvastatin treatment upregulated eNOS expression and reduced the interaction of cytosolic protein with the 3'-untranslated region of eNOS mRNA.
  
  
  CONCLUSIONS
  These results demonstrate the presence of a 60-KDa protein that binds to eNOS mRNA and reduces eNOS expression in the vascular wall.
authors.affiliation: Laboratorio de Investigación Cardiovascular e Hipertensión. Fundación Jiménez Díaz. Madrid. España.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Jiménez
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Millás
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Farré
authors.forename: Antonio
authors.initials: A
authors.lastname: García-Méndez
authors.forename: Petra
authors.initials: P
authors.lastname: Jiménez
authors.forename: María M
authors.initials: MM
authors.lastname: Arriero
authors.forename: Elena
authors.initials: E
authors.lastname: García-Colis
authors.forename: Raimundo
authors.initials: R
authors.lastname: de Andrés
authors.forename: Juan
authors.initials: J
authors.lastname: Gómez
authors.forename: Santos
authors.initials: S
authors.lastname: Casado
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Farré
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D019821:Simvastatin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III