Calcific Aortic Valve Stenosis in Old Hypercholesterolemic Mice

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Abstract
Background— Hypercholesterolemia and old age are clinical risk factors for development of aortic valve stenosis, and hypercholesterolemia is a putative therapeutic target. We tested the hypothesis that calcification and aortic valve stenosis would develop in genetically hypercholesterolemic old mice. Methods and Results— Twenty-four low-density lipoprotein receptor–deficient apolipoprotein B-100–only (LDLr−/−ApoB100/100) mice were fed normal chow from weaning until age 20.1±0.5 months (mean±SE; range 17 to 22 months). Twenty-one age-matched (20.8±0.9 months, range 17 to 25 months) C57Bl/6 mice served as controls. Echocardiographic imaging was used to assess morphology and function of the aortic valve and left ventricle. A subset of 12 mice underwent invasive hemodynamic assessment of aortic valve function. Functionally significant aortic stenosis, with >75% reduction in valve area, occurred in 8 of 24 LDLr−/−ApoB100/100 mice and in 0 of 21 controls (P=0.01). In the subset that underwent catheterization, m...

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