title: Effects of an angiotensin II type 1 receptor blocker on aortic valve sclerosis in a preclinical model.
abstract: BACKGROUND
  Aortic valve sclerosis (AVS) is a chronic progressive disease involving lipid infiltration, inflammation, and tissue calcification. Despite its high prevalence, there are currently no clinically approved pharmaceuticals for the management of AVS. The objective of the current study was to elucidate the effects of an angiotensin II type 1 receptor blocker, alone or in combination with statin therapy, on the progression of AVS.
  
  
  METHODS
  Male New Zealand white rabbits were fed an atherogenic diet for a period of 12 months to induce AVS. Once disease was established, rabbits were randomly assigned to receive no treatment, olmesartan medoxomil, atorvastatin calcium, or a combination of both drugs for a period of 6 months. Disease progression was monitored in vivo using clinically relevant magnetic resonance imaging, and aortic valve cusps were examined ex vivo using histologic and immunohistochemical methods.
  
  
  RESULTS
  Cusp thickness significantly increased (0.58 ± 0.03 vs 0.39 ± 0.03 mm for cholesterol and control animals, respectively; P < 0.0001) and all classic hallmarks of disease progression-including lipid infiltration, inflammation, and tissue calcification-were observed after 12 months. Unfortunately, neither olmesartan medoxomil nor atorvastatin calcium were able to reverse or delay disease progression during the 6-month treatment period. However, several histologic changes were observed in the valvular microenvironment.
  
  
  CONCLUSIONS
  The current study suggests that angiotensin receptor blockers, alone or in combination with statin therapy, may not be suitable for management of clinical AVS.
authors.affiliation: Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Zachary B
authors.initials: ZB
authors.lastname: Armstrong
authors.affiliation: Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Imaging Research Laboratories, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Derek R
authors.initials: DR
authors.lastname: Boughner
authors.affiliation: Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Colin P
authors.initials: CP
authors.lastname: Carruthers
authors.affiliation: Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; Imaging Research Laboratories, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Drangova
authors.affiliation: Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. Electronic address: kem.rogers@schulich.uwo.ca.
authors.forename: Kem A
authors.initials: KA
authors.lastname: Rogers
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D001021:Aortic Valve / Q000473:pathology; D000069059:Atorvastatin; D000082882:Bicuspid Aortic Valve Disease; D018450:Disease Progression; D006330:Heart Defects, Congenital / Q000188:drug therapy* / Q000473:pathology; D006349:Heart Valve Diseases / Q000188:drug therapy* / Q000473:pathology; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use; D011817:Rabbits; D011897:Random Allocation; D012598:Sclerosis / Q000188:drug therapy; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D057911:Angiotensin Receptor Antagonists; D006538:Heptanoic Acids; D007093:Imidazoles; D011758:Pyrroles; D013777:Tetrazoles; C437965:olmesartan; D000069059:Atorvastatin