Abstract 3035: Decrease Of Aortic Valve Area In A Hypercholesterolemic Rabbit Model Is Reversed By Short-term ApoAI-treatment
Background. Aortic valve stenosis (AVS) is the second most common indication for heart surgery. Althoug recent observations linked AVS and atherosclerosis, medical treatment of AVS is limited. ApoAI-Milano (ApoAI-M) is a mutant form of ApoAI. We have recently shown that ApoAI-M rapidly regressed established atherosclerotic lesions in a hypercholesteremic rabbit model. The aim of this study was to test whether hypercholestermia decreases AVA in rabbits and whether this can be reversed by short-term ApoAI-M-treatment.
Methods. We used transthoracic echocardiography (Philips HD 11 XE echograph with a 12-MHz phased-array probe) to compare AVA, as determined by continuity equation, of 14 white New Zeeland rabbits, fed with atherogenic diet (0.2 % of cholesterol) for nine month, with 6 healthy controls. The hypercholesterolemic animals were then randomized into ApoAI-M (ETC-216; Pfizer): 2 injections (75mg/Kg) in 4 days, or placebo. Six days after the last dose, we assessed aortic valve morphology by echocardiography and histopathology.
Results. Hypercholesteremic diet resulted in a markedly reduced AVA compared to controls (0.17±0.02cm2 vs. 0.21±0.03cm2, p<0.01). ApoAI-M treatment increased AVA by 27 % (p<0.05) whereas placebo had no effect, resulting in significantly higher AVA in treated rabbits (0.22±0.03cm2 vs 0.16±0.02cm2, p<0.005). Histopathologic cross-examination showed markedly reduced thickness of aortic valve leaflets in ApoAI-M-treated rabbits.
Conclusion. We show that reduction of AVA can be induced experimentally in hypercholesterolemic rabbits and can be investigated by transthoracic echocardiography. In addition, this study provides for the first time evidence that AVA can be increased pharmacologically, namely by treatment with ApoAI-M.