High-cholesterol + vitamin D2 regimen: a questionable in-vivo experimental model of aortic valve stenosis.
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.
Hekimian
Guillaume
G
INSERM U698, AP-HP, Bichat Hospital, Paris, France.
Passefort
Stephanie
S
Louedec
Liliane
L
Houard
Xavier
X
Jacob
Marie-Paule
MP
Vahanian
Alec
A
Michel
Jean-Bapstiste
JB
Messika-Zeitoun
David
D
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*
D002791:Cholesterol, Dietary; D004872:Ergocalciferols; D014815:Vitamins