Rapid Change in Plaque Size, Composition, and Molecular Footprint After Recombinant Apolipoprotein A-IMilano (ETC-216) AdministrationMagnetic Resonance Imaging Study in an Experimental Model of Atherosclerosis
Borja Ibanez, MD*,
Gemma Vilahur, DVM, PhD ,
Giovanni Cimmino, MD*,
Walter S. Speidl, MD*,
Antonio Pinero, MD*,
Brian G. Choi, MD*,
M. Urooj Zafar, MD*,
Carlos G. Santos-Gallego, MD*,
Brian Krause, PhD ,
Lina Badimon, PhD,
Valentin Fuster, MD, PhD, FACC* and
Juan J. Badimon, PhD, FACC*
* Cardiovascular Biology Research Laboratory, Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York
Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, UAB, Barcelona, Spain
Pfizer Research and Development, Groton, Connecticut.
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Figure 1 Atherosclerotic Plaque Regression in an Animal Receiving Recombinant apoA-IMilano
Magnetic resonance images before (A) and after (B) treatment at the same level of the abdominal aorta. (C and D) The same images as panels A and B but highlighting the autotracing of luminal and total vessel area contours. (E and F) Magnification of panels A and B drawing the plaque area. Plaque size in this segment regressed by 20.5% after 2 doses of apoA-IMilano. apo = apolipoprotein.
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Figure 2 Gelatinolytic Activity of Atherosclerotic Lesions in Animals Receiving rApoA-IM
Zymography performed in atherosclerotic lesions shows a markedly reduced gelatinase activity after rApoA-IMilano administration compared with placebo. apo = apolipoprotein; rApoA-IM = recombinant apolipoprotein A-IMilano.
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Figure 3 Protein Expression in Aortic Lesions by Western Blot
Recombinant apoA-IMilano administration resulted in a significant antigen down-regulation of TF, MCP-1, and COX-2. Conversely, COX-1 was up-regulated in recombinant apoA-IMilano animals compared with placebo. aA-IM = apolipoprotein A-IMilano; apo = apolipoprotein; COX = cyclooxygenase; MCP = monocyte chemoattractant protein; Plac = placebo; TF = tissue factor.
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Figure 4 COX-1 and COX-2 Gene Expression in Aortic Lesions by Polymerase Chain Reaction
Recombinant apoA-IMilano administration resulted in COX-1 gene up-regulation and COX-2 gene down-regulation. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as the housekeeping gene. bp = base pairs; other abbreviations as in Figure 3.
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