Abstract
Objectives: This study sought to evaluate in vivo the minimal dose of apolipoprotein (apo) A-IMilano phospholipid complex (recombinant apoA-IMilano and 1-palmitoyl-2-oleoyl phosphatidylcholine complexes [ETC-216]) able to induce atherosclerosis regression in a rabbit model of lipid-rich plaques. Background: A single high dose of recombinant apoA-IMilano has promoted atherosclerosis regression in animal models. More recently, regression of atherosclerosis was achieved in coronary patients by repeated infusions of ETC-216. Methods: Thirty-six rabbits underwent perivascular injury at both carotid arteries, followed by a 1.5% cholesterol diet. After 90 days, rabbits were randomly divided into 6 groups and treated 5 times with vehicle or ETC-216 at 5, 10, 20, 40, or 150 mg/kg dose every 4 days. Carotid plaque changes were evaluated in vivo by intravascular ultrasound (IVUS) and magnetic resonance imaging (MRI), performed before and at the end of treatments. Magnetic resonance imaging scans were also recorded after administration of the second dose for rabbits infused with vehicle 40 or 150 mg/kg. Results: Atheroma volume in vehicle-treated rabbits increased dramatically between the first and the second IVUS analyses (+26.53%), whereas in ETC-216-treated animals, a reduced progression at the lower doses and a significant regression at the higher doses, up to -6.83%, was detected. Results obtained by MRI analysis correlated significantly with those at IVUS (r = 0.706; p <0.0001). The MRI evaluations after the second infusion established that a significant regression was achieved with only 2 administrations of the highest dose. Conclusions: These results confirm the efficacy of ETC-216 for atherosclerosis treatment and provide guidance for dose selection and frequency to obtain a significant reduction of plaque volume.
| Original language | English |
|---|---|
| Pages (from-to) | 1098-1103 |
| Number of pages | 6 |
| Journal | Journal of the American College of Cardiology |
| Volume | 51 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Mar 18 2008 |
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Dose-Related Effects of Repeated ETC-216 (Recombinant Apolipoprotein A-IMilano/1-Palmitoyl-2-Oleoyl Phosphatidylcholine Complexes) Administrations on Rabbit Lipid-Rich Soft Plaques. In Vivo Assessment by Intravascular Ultrasound and Magnetic Resonance Imaging. / Parolini, Cinzia; Marchesi, Marta; Lorenzon, Paolo; Castano, Mauro; Balconi, Elena; Miragoli, Luigi; Chaabane, Linda; Morisetti, Alberto; Lorusso, Vito; Martin, Bradley J.; Bisgaier, Charles L.; Krause, Brian; Newton, Roger S.; Sirtori, Cesare R.; Chiesa, Giulia.
In: Journal of the American College of Cardiology, Vol. 51, No. 11, 18.03.2008, p. 1098-1103.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Dose-Related Effects of Repeated ETC-216 (Recombinant Apolipoprotein A-IMilano/1-Palmitoyl-2-Oleoyl Phosphatidylcholine Complexes) Administrations on Rabbit Lipid-Rich Soft Plaques. In Vivo Assessment by Intravascular Ultrasound and Magnetic Resonance Imaging
AU - Parolini, Cinzia
AU - Marchesi, Marta
AU - Lorenzon, Paolo
AU - Castano, Mauro
AU - Balconi, Elena
AU - Miragoli, Luigi
AU - Chaabane, Linda
AU - Morisetti, Alberto
AU - Lorusso, Vito
AU - Martin, Bradley J.
AU - Bisgaier, Charles L.
AU - Krause, Brian
AU - Newton, Roger S.
AU - Sirtori, Cesare R.
AU - Chiesa, Giulia
PY - 2008/3/18
Y1 - 2008/3/18
N2 - Objectives: This study sought to evaluate in vivo the minimal dose of apolipoprotein (apo) A-IMilano phospholipid complex (recombinant apoA-IMilano and 1-palmitoyl-2-oleoyl phosphatidylcholine complexes [ETC-216]) able to induce atherosclerosis regression in a rabbit model of lipid-rich plaques. Background: A single high dose of recombinant apoA-IMilano has promoted atherosclerosis regression in animal models. More recently, regression of atherosclerosis was achieved in coronary patients by repeated infusions of ETC-216. Methods: Thirty-six rabbits underwent perivascular injury at both carotid arteries, followed by a 1.5% cholesterol diet. After 90 days, rabbits were randomly divided into 6 groups and treated 5 times with vehicle or ETC-216 at 5, 10, 20, 40, or 150 mg/kg dose every 4 days. Carotid plaque changes were evaluated in vivo by intravascular ultrasound (IVUS) and magnetic resonance imaging (MRI), performed before and at the end of treatments. Magnetic resonance imaging scans were also recorded after administration of the second dose for rabbits infused with vehicle 40 or 150 mg/kg. Results: Atheroma volume in vehicle-treated rabbits increased dramatically between the first and the second IVUS analyses (+26.53%), whereas in ETC-216-treated animals, a reduced progression at the lower doses and a significant regression at the higher doses, up to -6.83%, was detected. Results obtained by MRI analysis correlated significantly with those at IVUS (r = 0.706; p <0.0001). The MRI evaluations after the second infusion established that a significant regression was achieved with only 2 administrations of the highest dose. Conclusions: These results confirm the efficacy of ETC-216 for atherosclerosis treatment and provide guidance for dose selection and frequency to obtain a significant reduction of plaque volume.
AB - Objectives: This study sought to evaluate in vivo the minimal dose of apolipoprotein (apo) A-IMilano phospholipid complex (recombinant apoA-IMilano and 1-palmitoyl-2-oleoyl phosphatidylcholine complexes [ETC-216]) able to induce atherosclerosis regression in a rabbit model of lipid-rich plaques. Background: A single high dose of recombinant apoA-IMilano has promoted atherosclerosis regression in animal models. More recently, regression of atherosclerosis was achieved in coronary patients by repeated infusions of ETC-216. Methods: Thirty-six rabbits underwent perivascular injury at both carotid arteries, followed by a 1.5% cholesterol diet. After 90 days, rabbits were randomly divided into 6 groups and treated 5 times with vehicle or ETC-216 at 5, 10, 20, 40, or 150 mg/kg dose every 4 days. Carotid plaque changes were evaluated in vivo by intravascular ultrasound (IVUS) and magnetic resonance imaging (MRI), performed before and at the end of treatments. Magnetic resonance imaging scans were also recorded after administration of the second dose for rabbits infused with vehicle 40 or 150 mg/kg. Results: Atheroma volume in vehicle-treated rabbits increased dramatically between the first and the second IVUS analyses (+26.53%), whereas in ETC-216-treated animals, a reduced progression at the lower doses and a significant regression at the higher doses, up to -6.83%, was detected. Results obtained by MRI analysis correlated significantly with those at IVUS (r = 0.706; p <0.0001). The MRI evaluations after the second infusion established that a significant regression was achieved with only 2 administrations of the highest dose. Conclusions: These results confirm the efficacy of ETC-216 for atherosclerosis treatment and provide guidance for dose selection and frequency to obtain a significant reduction of plaque volume.
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U2 - 10.1016/j.jacc.2007.12.010
DO - 10.1016/j.jacc.2007.12.010
M3 - Article
VL - 51
SP - 1098
EP - 1103
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
SN - 0735-1097
IS - 11
ER -