Abstract 6143: Regression of Aortic Valve Stenosis by ApoA-I Mimetic Peptide Infusions in Rabbits
Purpose: Aortic valve stenosis is the most common valvular heart disease, and standard curative therapy remains open-heart surgical valve replacement. The aim of our experimental study was to determine if ApoA-I mimetic peptide infusions could induce regression of aortic valve stenosis.
Methods: Twenty-seven New-Zealand White male rabbits received a cholesterol-enriched diet and vitamin D2 until significant aortic valve stenosis was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were randomized to receive saline (control group, n=14) or an ApoA-I mimetic peptide (treated group, n=13), 3 times per week for 2 weeks. Serial echocardiograms and post mortem valve histology were performed.
Results: Aortic valve area improved significantly in the treated group compared to controls after 7 days (20.9±0.9 mm2 vs. 18.2±0.6 mm2, P<0.0001) (corresponding to increases of 15.9% and 1.9%), 10 days (21.5±1.0 mm2 vs. 19.5±0.6 mm2, P=0.0032) (increases of 19.2% vs. 9.1%), and 14 days of treatment (22.4±0.9 mm2 vs. 20.4±0.6 mm2, P=0.0028) (increases of 24.4% vs. 14.2%). Likewise, aortic valve thickness decreased by 19% after 14 days of treatment in the treated group (0.951±0.070 mm at baseline vs. 0.768±0.074 mm at follow-up) whereas it was unchanged in controls (P<0.0001). Histological analysis revealed that lesion extent at the base of valve leaflets and sinuses of Valsalva was smaller in the treated compared to control group (52.8±12.5% vs. 66.7±9.9%, P=0.032). The ApoA-I mimetic peptide treatment also leads to a reduction in aortic valve calcifications as revealed by the loss of the positive relationship observed in the control group (r=0.87, P=0.004) between calcifications area and aortic valve thickness.
Conclusions: Infusions of an ApoA-I mimetic peptide lead to regression of experimental aortic valve stenosis. These positive results justify the further testing of HDL-based therapies in patients with valvular aortic stenosis. Regression of aortic stenosis, if achieved safely, could transform our clinical approach of this disease.