title: High-cholesterol + vitamin D2 regimen: a questionable in-vivo experimental model of aortic valve stenosis.
abstract: OBJECTIVE
  Recent data have shown that aortic valve stenosis (AS) is an active and highly regulated process which shares similarities with atherosclerosis. However, AS cannot be considered as a purely atherosclerotic phenomenon, and a hypercholesterolemic rabbit model might not be fully representative of human AS pathophysiology.
  
  
  METHODS
  Twenty-eight New Zealand White rabbits were assigned to three groups: group 1 (no dietary supplement for three months); group 2 (0.3% cholesterol-enriched-diet + 50,000 IU/day vitamin D2 for six months); and group 3 (1% cholesterol-enriched-diet + vitamin D2 for three months). The peak aortic gradient and permeability index (outflow tract/aortic velocity-time-integral) were assessed, as well as calcium staining within the aortic valve and ascending aorta.
  
  
  RESULTS
  AS hemodynamic severity was not different among the groups. The peak gradient was 4 +/- 2 mmHg at baseline, 4 +/- 2 mmHg at three months in controls, 4 +/- 1 mmHg at three months and 6 +/-3 mmHg at six months in group 2, and 4 +/- 1 mmHg at three months in group 3 (p = NS). The permeability index was 64 +/- 7 at baseline, 60 +/- 12 at three months in controls, 63 +/- 14 at three months and 58 +/- 12 at six months in group 2, and 60 +/- 5 at three months in group 3 (p = NS). The aortic valve of cholesterol-enriched-diet rabbits was thickened but not calcified, whereas the ascending aorta was both thickened and calcified.
  
  
  CONCLUSIONS
  When using a hypercholesterolemic rabbit model plus vitamin D2, no adverse hemodynamic effect or aortic valve calcification was observed, despite a high-level and prolonged cholesterol-regimen supplementation. These results raise questions with regard to the extrapolation of this animal model to humans.
authors.affiliation: INSERM U698, AP-HP, Bichat Hospital, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Hekimian
authors.forename: Stephanie
authors.initials: S
authors.lastname: Passefort
authors.forename: Liliane
authors.initials: L
authors.lastname: Louedec
authors.forename: Xavier
authors.initials: X
authors.lastname: Houard
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Jacob
authors.forename: Alec
authors.initials: A
authors.lastname: Vahanian
authors.forename: Jean-Bapstiste
authors.initials: JB
authors.lastname: Michel
authors.forename: David
authors.initials: D
authors.lastname: Messika-Zeitoun
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001024:Aortic Valve Stenosis / Q000503:physiopathology*; D050197:Atherosclerosis / Q000473:pathology; D001783:Blood Flow Velocity; D002114:Calcinosis / Q000473:pathology; D002199:Capillary Permeability; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004872:Ergocalciferols / Q000008:administration & dosage*; D008297:Male; D008853:Microscopy; D023421:Models, Animal; D011817:Rabbits; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D002791:Cholesterol, Dietary; D004872:Ergocalciferols; D014815:Vitamins