title: Aliskiren inhibits atherosclerosis development and improves plaque stability in APOE*3Leiden.CETP transgenic mice with or without treatment with atorvastatin.
abstract: OBJECTIVE
  Aliskiren is the first commercially available, orally active, direct renin inhibitor approved to treat hypertension. The renin-angiotensin system has been shown to be a significant contributor to the development of hypercholesterolemia-induced atherosclerosis. The aim of this study was to evaluate the antiatherosclerotic and plaque stabilization effects of aliskiren alone and in combination with atorvastatin.
  
  
  METHODS
  APOE*3Leiden.CETP mice (n = 14-17/group) were fed a western-type diet (containing 0.25% cholesterol) alone or were treated with either aliskiren (15 mg/kg per day), atorvastatin (3.6 mg/kg per day) or a combination of aliskiren and atorvastatin. Effects on SBP, total cholesterol, inflammation markers and atherosclerotic size and composition were assessed.
  
  
  RESULTS
  Aliskiren reduced SBP (-19%, P < 0.001) and atorvastatin reduced total cholesterol (-24%, P < 0.001). Atherosclerotic lesion area was reduced by aliskiren (-40%, P < 0.01), atorvastatin (-61%, P < 0.001) and the combination treatment (-69%, P < 0.001). Aliskiren alone and together with atorvastatin decreased the number of T cells in the aortic root area (-60%, P < 0.01; -41%, P < 0.05), as well as macrophage (-64%, P < 0.001; -72%, P < 0.001) and necrotic area (-52%, P = 0.071; -84%, P < 0.001) in the lesion. Atorvastatin alone and together with aliskiren decreased monocyte adherence (-43%, P < 0.05 and -51%, P < 0.01) and monocyte chemoattractant protein-1 (both -36%, P < 0.01). The combination treatment decreased the number of lesions (-17%, P < 0.05) and E-selectin (-17%, P < 0.05).
  
  
  CONCLUSIONS
  Aliskiren inhibited atherosclerosis development and improved plaque stability alone and in combination with atorvastatin, possibly via a mechanism involving T cells. These results suggest a potential benefit of using aliskiren in a clinical setting, particularly in combination with statin treatment.
authors: TNO Metabolic Health Research, Leiden University Medical Center, Leiden, The Netherlands. susan.jordaan@tno.nl
authors: Susan
authors: S
authors: Kühnast
authors: José W A
authors: JW
authors: van der Hoorn
authors: Anita M
authors: AM
authors: van den Hoek
authors: Louis M
authors: LM
authors: Havekes
authors: Gene
authors: G
authors: Liau
authors: J Wouter
authors: JW
authors: Jukema
authors: Hans M G
authors: HM
authors: Princen
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000517:prevention & control*; D000069059:Atorvastatin; D005260:Female; D005650:Fumarates / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: D000577:Amides; D001057:Apolipoproteins E; D005650:Fumarates; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; C446481:aliskiren; D000069059:Atorvastatin