title: Statin treatment of hypercholesterolemic-induced aortic valve sclerosis.
abstract: BACKGROUND
  Aortic valve sclerosis (AVS) is a common inflammatory heart valve disease prevalent in the population over the age of 65 years. Several published clinical and animal studies have examined the ability of statin treatment to modify disease progression. Clinical trials yielded conflicting results, and animal studies examined the effects of statins prior to the onset of disease. Our study assessed the effect of dietary modification and/or statin treatment on established aortic valve disease in a rabbit model of AVS to examine the tissue response to therapy.
  
  
  METHODS
  Aortic valve sclerosis was induced in male New Zealand White rabbits by dietary cholesterol supplementation. Rabbits were followed over 2.5 years, with the introduction of statins and/or dietary changes for the second half of the study. At end point, valve function was examined by magnetic resonance imaging. Excised aortic valve cusp tissue was surveyed for thickness, lipid accumulation, protein deposition, calcification, and cellular infiltration.
  
  
  RESULTS
  By 15 months, cholesterol-fed valves exhibited thickening due to significant lipid content, macrophage infiltration, and osteopontin expression. By 30 months, the untreated disease had progressed to include elevated collagen deposition, lymphocyte invasion, and calcification. With treatment, however, the valve cusps exhibited significant pathological changes including diminished immune cell infiltration and osteopontin expression. Unfortunately, lipid was retained and calcification persisted in all treated valves.
  
  
  CONCLUSIONS
  In established AVS, the cellular response to statin therapy does not result in full regression of the sclerotic process.
authors.affiliation: Department of Anatomy and Cell Biology, The University of Western Ontario, London, ON, Canada.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Hamilton
authors.forename: Derek R
authors.initials: DR
authors.lastname: Boughner
authors.forename: Maria
authors.initials: M
authors.lastname: Drangova
authors.forename: Kem A
authors.initials: KA
authors.lastname: Rogers
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000187:drug effects / Q000473:pathology*; D006349:Heart Valve Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D011817:Rabbits; D012598:Sclerosis
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors