TY - JOUR
T1 - Rapid Change in Plaque Size, Composition, and Molecular Footprint After Recombinant Apolipoprotein A-IMilano (ETC-216) Administration. Magnetic Resonance Imaging Study in an Experimental Model of Atherosclerosis
AU - Ibanez, Borja
AU - Vilahur, Gemma
AU - Cimmino, Giovanni
AU - Speidl, Walter S.
AU - Pinero, Antonio
AU - Choi, Brian G.
AU - Zafar, M. Urooj
AU - Santos-Gallego, Carlos G.
AU - Krause, Brian
AU - Badimon, Lina
AU - Fuster, Valentin
AU - Badimon, Juan J.
N1 - Funding Information:
This work has been partially funded by Pfizer Research & Development. Dr. Ibanez has received a grant from the Working Group on Ischemic Heart Disease of the Spanish Society of Cardiology. Dr. Vilahur has received a grant from the Science-Education Spanish Ministry. Dr. Badimon has served as a consultant for Pfizer.
PY - 2008/3/18
Y1 - 2008/3/18
N2 - Objectives: This study sought to assess the effect of short-term apolipoprotein (apo) A-IMilano administration on plaque size and on suspected markers of plaque vulnerability. Background: Long-term lipid-lowering interventions can regress and stabilize atherosclerotic plaques. However, the majority of recurrent events occur early after the first episode. Interventions able to acutely induce plaque regression and stabilization are lacking. Regression of human coronary lesions after 5 weeks of treatment with apoA-IMilano administration has been shown. However, there are no data regarding its effect on plaque vulnerability. Methods: Advanced aortic lesions were induced in New Zealand White rabbits (n = 40). Plaque size was assessed by magnetic resonance imaging (MRI) at the end of atherosclerosis induction. Animals were randomized to placebo or apoA-IMilano phospholipids (ETC-216), 2 infusions 4 days apart. After the last dose, another MRI study was performed and aortas were processed for cellular composition and gene protein expression of markers associated with plaque instability. Results: Pre-treatment MRI showed similar plaque size in both groups, whereas post-treatment MRI showed 6% smaller plaques in apoA-IMilano-treated animals compared with placebo (p = 0.026). The apoA-IMilano treatment induced a 5% plaque regression (p = 0.003 vs. pre-treatment), whereas the placebo showed no significant effect. Plaque regression by apoA-IMilano was associated with a reduction in plaque macrophage density and a significant down-regulation in gene and protein expression of tissue factor, monocyte chemoattractant protein-1, and cyclooxygenase-2, as well as marked decrease in gelatinolytic activity. Conversely, cyclooxygenase-1 was significantly up-regulated. Conclusions: Acute plaque regression observed after short-term apoA-IMilano administration was associated with a significant reduction in suspected makers of plaque vulnerability in an experimental model of atherosclerosis.
AB - Objectives: This study sought to assess the effect of short-term apolipoprotein (apo) A-IMilano administration on plaque size and on suspected markers of plaque vulnerability. Background: Long-term lipid-lowering interventions can regress and stabilize atherosclerotic plaques. However, the majority of recurrent events occur early after the first episode. Interventions able to acutely induce plaque regression and stabilization are lacking. Regression of human coronary lesions after 5 weeks of treatment with apoA-IMilano administration has been shown. However, there are no data regarding its effect on plaque vulnerability. Methods: Advanced aortic lesions were induced in New Zealand White rabbits (n = 40). Plaque size was assessed by magnetic resonance imaging (MRI) at the end of atherosclerosis induction. Animals were randomized to placebo or apoA-IMilano phospholipids (ETC-216), 2 infusions 4 days apart. After the last dose, another MRI study was performed and aortas were processed for cellular composition and gene protein expression of markers associated with plaque instability. Results: Pre-treatment MRI showed similar plaque size in both groups, whereas post-treatment MRI showed 6% smaller plaques in apoA-IMilano-treated animals compared with placebo (p = 0.026). The apoA-IMilano treatment induced a 5% plaque regression (p = 0.003 vs. pre-treatment), whereas the placebo showed no significant effect. Plaque regression by apoA-IMilano was associated with a reduction in plaque macrophage density and a significant down-regulation in gene and protein expression of tissue factor, monocyte chemoattractant protein-1, and cyclooxygenase-2, as well as marked decrease in gelatinolytic activity. Conversely, cyclooxygenase-1 was significantly up-regulated. Conclusions: Acute plaque regression observed after short-term apoA-IMilano administration was associated with a significant reduction in suspected makers of plaque vulnerability in an experimental model of atherosclerosis.
UR - http://www.scopus.com/inward/record.url?scp=40649089928&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2007.09.071
DO - 10.1016/j.jacc.2007.09.071
M3 - Article
C2 - 18342230
AN - SCOPUS:40649089928
SN - 0735-1097
VL - 51
SP - 1104
EP - 1109
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 11
ER -