title: ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model.
abstract: BACKGROUND
  We examined whether impaired renal function causes thickening of the aortic valve leaflets in hyperlipidemic apoE-knockout (apoE-/-) mice, and whether the putative effect on the aortic valves could be prevented by inhibiting the angiotensin-converting enzyme (ACE) with enalapril.
  
  
  METHODS
  Thickening of the aortic valve leaflets in apoE-/- mice was induced by producing mild or moderate chronic renal failure resulting from unilateral nephrectomy (1/2 NX, n = 18) or subtotal nephrectomy (5/6 NX, n = 22), respectively. Additionally, the 5/6 NX mice were randomized to no treatment (n = 8) or enalapril treatment (n = 13). The maximal thickness of each leaflet was measured from histological sections of the aortic roots.
  
  
  RESULTS
  Leaflet thickness was significantly greater in the 5/6 NX mice than in the 1/2 NX mice (P = 0.030) or the unoperated mice (P = 0.003). The 5/6 NX mice treated with enalapril had significantly thinner leaflets than did the untreated 5/6 NX mice (P = 0.014).
  
  
  CONCLUSIONS
  Moderate uremia causes thickening of the aortic valves in apoE-/- mice, which can be attenuated by ACE inhibition. The nephrectomized apoE-/- mouse constitutes a new model for investigating the mechanisms of uremia-induced aortic valve disease, and also provides an opportunity to study its pharmacologic prevention.
authors.affiliation: Wihuri Research Institute, Helsinki, Finland. mikko.simolin@helsinki.fi
authors.forename: Mikko A
authors.initials: MA
authors.lastname: Simolin
authors.forename: Tanja X
authors.initials: TX
authors.lastname: Pedersen
authors.forename: Susanne
authors.initials: S
authors.lastname: Bro
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Mäyränpää
authors.forename: Satu
authors.initials: S
authors.lastname: Helske
authors.forename: Lars B
authors.initials: LB
authors.lastname: Nielsen
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D001021:Aortic Valve / Q000473:pathology; D001024:Aortic Valve Stenosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004656:Enalapril / Q000008:administration & dosage*; D005355:Fibrosis / Q000188:drug therapy*; D006949:Hyperlipidemias; D007668:Kidney / Q000473:pathology / Q000601:surgery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009392:Nephrectomy; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects; D014508:Urea / Q000097:blood; D014511:Uremia
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001057:Apolipoproteins E; D004656:Enalapril; D014508:Urea; D003404:Creatinine