Dose-Related Effects of Repeated ETC-216 (Recombinant Apolipoprotein A-IMilano/1-Palmitoyl-2-Oleoyl Phosphatidylcholine Complexes) Administrations on Rabbit Lipid-Rich Soft PlaquesIn Vivo Assessment by Intravascular Ultrasound and Magnetic Resonance Imaging
Cinzia Parolini, PhD*,
Marta Marchesi, PhD*,
Paolo Lorenzon*,
Mauro Castano, PhD ,
Elena Balconi, BS*,
Luigi Miragoli,
Linda Chaabane, PhD,
Alberto Morisetti, BS,
Vito Lorusso, BS,
Bradley J. Martin, PhD ,
Charles L. Bisgaier, PhD,
Brian Krause, PhD,
Roger S. Newton, PhD,
Cesare R. Sirtori, MD, PhD* and
Giulia Chiesa, PhD*,*
* Department of Pharmacological Sciences, University of Milan, Milan, Italy
Bracco Imaging SpA, Colleretto Giacosa, Turin, Italy
Esperion Therapeutics, Pfizer Inc., Plymouth, Michigan.
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Figure 1 Absolute Values and Percent Changes Evaluated by IVUS
Absolute values (A) and percent change (B) of total atheroma volume evaluated by IVUS at the right carotid arteries in rabbits treated with vehicle (control) or different doses of ETC-216. Data are expressed as mean ± SEM. (A) Open bars represent pre-treatment; solid bars represent post-treatment. *p < 0.05 versus control post-treatment. (B)  p < 0.05 versus control; ¶p < 0.0005 versus ETC-216 at 5 mg/kg; #p < 0.05 versus ETC-216 at 10 mg/kg. ETC-216 = recombinant apolipoprotein A-IMilano and 1-palmitoyl-2-oleoyl phosphatidylcholine complexes; IVUS = intravascular ultrasound.
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Figure 2 Examples of IVUS Images of Atherosclerotic Plaques Acquired Before and After Treatment With Vehicle (Control) or 150 mg/kg ETC-216
Plaque areas are identified in yellow. A progression is visible in the control animal, whereas a regression is observed in the ETC-216–treated rabbit. Abbreviations as in Figure 1.
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Figure 3 Percent Change in Plaque Area at the Maximum Plaque Burden Evaluated by IVUS
Rabbits were treated with vehicle (control) or ETC-216. Data are expressed as mean ± SEM. p < 0.001 versus control; ¶p < 0.005 versus ETC-216 at 5 mg/kg; #p < 0.05 versus ETC-216 at 10 mg/kg. Abbreviations as in Figure 1.
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Figure 4 Absolute Values and Percent Changes Evaluated by MRI
Absolute values (A and C) and percent change (B and D) of total atheroma volume evaluated by MRI in rabbits treated five times with vehicle (control) or different doses of ETC-216. Data are expressed as mean ± SEM. (A and C) Open bars represent pre-treatment; solid bars represent post-treatment. *p < 0.05 versus control post-treatment; ^p < 0.05 versus ETC-216 at 5 mg/kg. (B and D) p < 0.05 versus control; ¶p < 0.05 versus ETC-216 at 5 mg/kg. MRI = magnetic resonance imaging; other abbreviations as in Figure 1.
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Figure 5 Examples of T2-Weighted Magnetic Resonance Images of Carotid Arteries Acquired at the Same Level Before and After Treatments With Vehicle (Control) or 150 mg/kg of ETC-216
Plaque areas are identified in yellow. A marked progression is visible in the control rabbit, whereas a regression is observed in the ETC-216-treated animal. Abbreviations as in Figure 1.
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Figure 6 Percent Change of Total Atheroma Volume at MRI After 2 and 5 Administrations
Percent change of total atheroma volume at right (A) and left (B) carotid arteries evaluated by MRI after 2 and 5 administrations of vehicle or ETC-216 (40 mg/kg and 150 mg/kg). Shaded bars represent effects of 2 administrations; solid bars represent effects of 5 administrations. Data are expressed as mean ± SEM. ¶p < 0.05 versus control after 2 administrations; p < 0.05 versus control after 5 administrations. Abbreviations as in Figures 1 and 4.
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Figure 7 Correlation Between IVUS and MRI Plaque Volume Percent Change at the RCAs
Solid triangles = control; open circles = 5 mg/kg ETC-216; solid diamonds = 10 mg/kg ETC-216; open squares = 20 mg/kg ETC-216; solid circles = 40 mg/kg ETC-216; open triangles = 150 mg/kg ETC-216 (r = 0.706; p < 0.0001). RCA = right carotid artery; other abbreviations as in Figures 1 and 4.
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