title: [Atorvastatin inhibits the atherosclerotic lesion induced by tumor necrosis factor-like weak inducer of apoptosis in apolipoprotein E deficient mice].
abstract: OBJECTIVE
  Interaction of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) with its receptor Fn14 accelerates atherosclerotic plaque development in ApoE deficient mice (ApoE KO). In this work, an analysis has been made on the effect of an HMG-CoA reductase inhibitor, atorvastatin, on atherosclerotic plaque development accelerated by TWEAK in ApoE KO mice.
  
  
  METHODS
  Eight week-old ApoE KO mice were fed with a high cholesterol diet for 4 weeks. The animals were then randomized into 3 groups: mice injected i.p. with saline, recombinant TWEAK (10 μg/kg/twice a week), or recombinant TWEAK plus atorvastatin (1 mg/kg/day) for 4 weeks. The lesion size, cellular composition, lipid and collagen content were analyzed, as well as inflammatory response in atherosclerotic plaques present in aortic root of mice.
  
  
  RESULTS
  TWEAK treated mice showed an increase in atherosclerotic plaque size, as well as in collagen/lipid ratio compared with control mice. In addition, macrophage content, MCP-1 and RANTES expression, and NF-κB activation were augmented in atherosclerotic plaques present in aortic root of TWEAK treated mice compared with control mice. Treatment with atorvastatin prevented all these changes induced by TWEAK in atherosclerotic lesions. Atorvastatin treatment also decreased Fn14 expression in the atherosclerotic plaques of ApoE KO mice.
  
  
  CONCLUSIONS
  Atorvastatin prevents the pro-atherogenic effects induced by TWEAK in ApoE KO mice, which could be related to the inhibition of Fn14 expression. The results of this study provide new information on the beneficial effects of statin treatment in cardiovascular diseases.
authors.affiliation: Laboratorio de Patología Vascular, Instituto de Investigación Sanitaria (ISS)-Fundación Jiménez Díaz, Madrid, España.
authors.forename: Valvanera
authors.initials: V
authors.lastname: Fernández-Laso
authors.affiliation: Laboratorio de Patología Vascular, Instituto de Investigación Sanitaria (ISS)-Fundación Jiménez Díaz, Madrid, España.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sastre
authors.affiliation: Laboratorio de Patología Vascular, Instituto de Investigación Sanitaria (ISS)-Fundación Jiménez Díaz, Madrid, España.
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.affiliation: Laboratorio de Patología Vascular, Instituto de Investigación Sanitaria (ISS)-Fundación Jiménez Díaz, Madrid, España.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Martín-Ventura
authors.affiliation: Laboratorio de Patología Vascular, Instituto de Investigación Sanitaria (ISS)-Fundación Jiménez Díaz, Madrid, España. Electronic address: lblanco@fjd.es.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Blanco-Colio
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D000069059:Atorvastatin / Q000494:pharmacology*; D000074049:Cytokine TWEAK; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000473:pathology / Q000517:prevention & control; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D000074049:Cytokine TWEAK; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D000074050:TWEAK Receptor; C000613299:Tnfrsf12a protein, mouse; C491645:Tnfsf12 protein, mouse; D048069:Tumor Necrosis Factors; D000069059:Atorvastatin
keywords: Aterosclerosis; Atherosclerosis, Tumor necrosis factor-like weak inducer apoptosis; Atorvastatin; Atorvastatina; Factor inductor débil de apoptosis similar al factor de necrosis tumoral; Inflamación; Inflammation