Dose-Related Effects of Repeated ETC-216 (Recombinant Apolipoprotein A-IMilano/1-Palmitoyl-2-Oleoyl Phosphatidylcholine Complexes) Administrations on Rabbit Lipid-Rich Soft Plaques
| Autor: | Roger S. Newton, Linda Chaabane, Charles L. Bisgaier, P. Lorenzon, Cinzia Parolini, Marta Marchesi, Luigi Miragoli, Cesare R. Sirtori, Alberto Morisetti, Bradley J. Martin, Elena Balconi, Mauro Castano, Giulia Chiesa, B.R. Krause, Vito Lorusso |
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| Rok vydání: | 2008 |
| Předmět: |
Pathology
medicine.medical_specialty medicine.diagnostic_test Apolipoprotein B biology business.industry Cholesterol Magnetic resonance imaging medicine.disease chemistry.chemical_compound Dose–response relationship Atheroma chemistry In vivo Intravascular ultrasound Circulatory system medicine biology.protein business Nuclear medicine Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of the American College of Cardiology. 51(11):1098-1103 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/j.jacc.2007.12.010 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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