title: Improvement of aortic valve stenosis by ApoA-I mimetic therapy is associated with decreased aortic root and valve remodelling in mice.
abstract: OBJECTIVE
  We have shown that infusions of apolipoprotein A-I (ApoA-I) mimetic peptide induced regression of aortic valve stenosis (AVS) in rabbits. This study aimed at determining the effects of ApoA-I mimetic therapy in mice with calcific or fibrotic AVS.
  
  
  METHODS
  Apolipoprotein E-deficient (ApoE(-/-) ) mice and mice with Werner progeria gene deletion (Wrn(Δhel/Δhel) ) received high-fat diets for 20 weeks. After developing AVS, mice were randomized to receive saline (placebo group) or ApoA-I mimetic peptide infusions (ApoA-I treated groups, 100 mg·kg(-1) for ApoE(-/-) mice; 50 mg·kg(-1) for Wrn mice), three times per week for 4 weeks. We evaluated effects on AVS using serial echocardiograms and valve histology.
  
  
  RESULTS
  Aortic valve area (AVA) increased in both ApoE(-/-) and Wrn mice treated with the ApoA-I mimetic compared with placebo. Maximal sinus wall thickness was lower in ApoA-I treated ApoE(-/-) mice. The type I/III collagen ratio was lower in the sinus wall of ApoA-I treated ApoE(-/-) mice compared with placebo. Total collagen content was reduced in aortic valves of ApoA-I treated Wrn mice. Our 3D computer model and numerical simulations confirmed that the reduction in aortic root wall thickness resulted in improved AVA.
  
  
  CONCLUSIONS
  ApoA-I mimetic treatment reduced AVS by decreasing remodelling and fibrosis of the aortic root and valve in mice.
authors: Montreal Heart Institute, Montreal, QC, Canada.
authors: J
authors: J
authors: Trapeaux
authors: D
authors: D
authors: Busseuil
authors: Y
authors: Y
authors: Shi
authors: S
authors: S
authors: Nobari
authors: D
authors: D
authors: Shustik
authors: M
authors: M
authors: Mecteau
authors: I
authors: I
authors: El-Hamamsy
authors: M
authors: M
authors: Lebel
authors: R
authors: R
authors: Mongrain
authors: E
authors: E
authors: Rhéaume
authors: J-C
authors: JC
authors: Tardif
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000000981:diagnostic imaging; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D016632:Apolipoprotein A-I / Q000008:administration & dosage*; D040761:Biomimetic Materials / Q000008:administration & dosage* / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D059305:Diet, High-Fat / Q000379:methods; D004195:Disease Models, Animal; D004562:Electrocardiography; D005786:Gene Expression Regulation; D006937:Hypercholesterolemia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000008:administration & dosage*; D014463:Ultrasonography
chemical_list: D016632:Apolipoprotein A-I; D010455:Peptides; D003094:Collagen
keywords: HDL; aortic valve stenosis; collagen; fibrosis; mouse model
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