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Updated: Jun 14, 2026
A Rabbit Aortic Valve Stenosis Model Induced by Direct Balloon Injury
Published on: March 31, 2023
Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and decreases leaflet inflammation in an
Walter S Speidl1, Giovanni Cimmino, Borja Ibanez
1Atherothrombosis Research Unit, Mount Sinai School of Medicine New York, NY, USA.
Aims:
Aortic stenosis (AS) is associated with significant morbidity and mortality. Recombinant apolipoprotein A-I Milano (rApoA-I(M)) induces atherosclerotic plaque regression. The aims of this study were to determine the effects of rApoA-I(M) on experimental aortic valve degeneration and its mechanisms of action.
Methods And Results:
New Zealand White rabbits (n = 20) were fed an atherogenic diet for 9 months and then randomized to either placebo or rApoA-I(M). Echocardiography was used to assess the effect of the treatments on AS. Porcine aortic valve myofibroblasts (PAVMF) treated with oxidized low-density lipoprotein served to define the effects of rApoA-I(M) on the expression of monocyte chemoattractant protein-1 (MCP-1), nuclear factor (NF)-kappaB, and alkaline phosphatase (AP). Recombinant apolipoprotein A-I Milano increased aortic valve area (AVA) by 32% (0.25 +/- 0.05 to 0.34 +/- 0.07 cm(2), P < 0.01); whereas AVA remained unchanged in the placebo group (0.24 +/- 0.05 to 0.26 +/- 0.04 cm(2), P = 0.58). Histopathological examination of aortic valves in the rApoA-I(M) animals showed significantly less leaflet thickening, inflammation, and calcification vs. the placebo group. In vitro, rApoA-I(M) significantly inhibited MCP-1, AP, and NF-kappaB and decreased intracellular cholesterol content in PAVMF.
Conclusion:
Recombinant apolipoprotein A-I Milano treatment reverses AS in this experimental rabbit model. The beneficial effects seem to be mediated by enhanced cholesterol removal and by reduced inflammation and calcification.
