title: Quinapril treatment abolishes diabetes-associated atherosclerosis in RAGE/apolipoprotein E double knockout mice.
abstract: Both the renin-angiotensin system (RAS) and the receptor for advanced glycation end products (RAGE) potentiate diabetes-associated atherosclerosis (DAA). We assessed the effectiveness of concomitant RAS and RAGE inhibition on DAA.
  
  
  METHODS
  Diabetic (5 × 55 mg/kg streptozotocin daily) and non-diabetic male RAGE/apolipoprotein E double knockout (RAGE/apoE DKO) mice were treated with quinapril (30 mg/kg/day) for 20 weeks. At the end of the study aortic plaques were assessed.
  
  
  RESULTS
  Diabetic RAGE/apoE DKO showed significantly less plaque area than diabetic apoE KO mice. Plaque deposition was almost abolished in quinapril treated diabetic RAGE/apoE DKOs, with significant attenuation of vascular collagen deposition, nitrotyrosine staining, and reduced macrophage infiltration. Expression of the advanced glycation end product receptor 3 (galectin 3) was also significantly reduced.
  
  
  CONCLUSIONS
  Concomitant inhibition of RAS and RAGE signalling almost completely inhibited the development of experimental DAA. A dual therapeutic approach may be a superior strategy for the treatment of diabetic macrovascular disease..
authors.affiliation: Diabetes Complications-Diabetes and The Kidney Laboratory, Baker IDI Heart and Diabetes Research Institute, Melbourne, Victoria, Australia. Electronic address: Anna.Watson@bakeridi.edu.au.
authors.forename: Anna M D
authors.initials: AM
authors.lastname: Watson
authors.affiliation: Diabetes Complications-Diabetes and The Kidney Laboratory, Baker IDI Heart and Diabetes Research Institute, Melbourne, Victoria, Australia.
authors.forename: Jiaze
authors.initials: J
authors.lastname: Li
authors.affiliation: Diabetes Complications-Diabetes and The Kidney Laboratory, Baker IDI Heart and Diabetes Research Institute, Melbourne, Victoria, Australia.
authors.forename: Dian
authors.initials: D
authors.lastname: Samijono
authors.affiliation: Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Bierhaus
authors.affiliation: Diabetes Complications-Diabetes and The Kidney Laboratory, Baker IDI Heart and Diabetes Research Institute, Melbourne, Victoria, Australia; Department of Medicine, Central Clinical School, Monash University, Australia.
authors.forename: Merlin C
authors.initials: MC
authors.lastname: Thomas
authors.affiliation: Diabetes Complications-Diabetes and The Kidney Laboratory, Baker IDI Heart and Diabetes Research Institute, Melbourne, Victoria, Australia; Department of Medicine, Central Clinical School, Monash University, Australia. Electronic address: karin.jandeleit-dahm@baker.edu.au.
authors.forename: Karin A M
authors.initials: KA
authors.lastname: Jandeleit-Dahm
authors.affiliation: Diabetes Complications-Diabetes and The Kidney Laboratory, Baker IDI Heart and Diabetes Research Institute, Melbourne, Victoria, Australia; Department of Medicine, Central Clinical School, Monash University, Australia.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000209:etiology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D008297:Male; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000517:prevention & control; D000077583:Quinapril; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000187:drug effects; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*
chemical_list: D001057:Apolipoproteins E; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D044005:Tetrahydroisoquinolines; D000077583:Quinapril
keywords: AGEs; Atherosclerosis; Experimental diabetes; Mouse model; RAGE